Safety and efficacy of a 48-week long-term ingestion of D-allulose in subjects with high LDL cholesterol levels

Abstract

-D-allulose is one of the rare sugars with almost zero calories and several health benefits. Previous studies have reported the safety of D-allulose in normal, overweight/obese, and diabetic humans. However, one study reported significant increases in T-Cho and LDL-C after 12 weeks of D-allulose intake; this report was not a randomized controlled trial and these changes were considered to be due to seasonal variations. We, therefore, conducted a randomized, double-blind, placebo-controlled trial in 90 subjects with high LDL-C levels for 48 weeks to clarify the influence of long-term D-allulose consumption on cholesterol metabolism and efficacy. Subjects were randomly divided into 3 groups: highdose D-allulose (15 g D-allulose/day), low-dose D-allulose (5 g D-allulose/day), and placebo group (0 g D-allulose/day); each subject consumed a daily test beverage for 48 weeks. Clinical examinations were performed every eight weeks, beginning from initial consumption until week 52. No significant increases in T-Cho and LDL-C between test groups were observed, and 48 weeks of D-allulose consumption did not change risk factors for atherosclerotic cardiovascular disease. Furthermore, no clinical problems were recognized for other parameters. Additionally, significant improvements in hepatic enzyme activities, fatty liver score, and glucose metabolism after long-term D-allulose consumption were observed. The results from our study revealed that 1) D-allulose consumption is considered safe for long-term intake up to a year, and 2) D-allulose may be effective for improving hepatic functions and glucose metabolism.

The influence of long-term ingestion of D-allulose in hypercholesterolemia patients under statin therapy

“…The declines from the initial values eventually disappeared in the follow-up period. HDL-C reductions with D-allulose intake have also been observed in previous studies (Tanaka et al, 2019(Tanaka et al, , 2020. Though low HDL-C levels are generally one of the risk factors for ASCVD, some reports indicate that low HDL-C does not necessarily lead to coronary heart disease risk (Rader et al, 1993;Hirata et al, 2016).…”

“…Improvement of hepatic function by D-allulose has been reported in previous studies (Hayashi et al, 2010;Itoh et al, 2015;Tanaka et al, 2019Tanaka et al, , 2020. In this study, all indicators associated with hepatic function (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase [γ-GTP] and alkaline phosphatase [ALP])…”

“…The degree of change was similar to a seasonal fluctuation or the effects by other food ingredients reported to increase LDL-C levels, such as n-3 fatty acid and the coffee diterpene cafestol (Harris, 1996;Mori et al, 2000;Urgert et al, 1997). However, because this study was an open trial without a placebo group, thereafter, a randomized controlled trial was conducted for 48 weeks in patients with borderline hyper-LDL cholesterolemia to clarify the influence of D-allulose on LDL-C (Tanaka et al, 2020). There were no significant differences in LDL-C levels among the groups.…”

“…Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have currently drawn attention as a drug used with statin because high doses of statin increases both LDL receptors and PCSK9, which degrades the LDL receptors (Mabuchi and Nohara, 2015). In previous studies, D-allulose reduces blood PCSK9 levels (Kanasaki et al, 2019;Tanaka et al, 2020); therefore, the combination of statin and D-allulose may contribute to lowering LDL-C levels. Meanwhile, significant decreases in HDL-C were observed in the D-allulose group compared to those in both week 0 and the placebo group (Table 2).…”

“…Many previous studies have demonstrated that D-allulose inhibits blood glucose elevation after meals (Hayashi et al, 2010;Iida et al, 2008) by the suppression of α-glucosidase activity in the gut (Matsuo and Izumori, 2006) and facilitation of glucokinase trans-location in the liver (Hossain et al, 2011). Long-term D-allulose consumption improves glucose metabolism in patients with borderline diabetes (Tanaka et al, 2020). D-allulose also declines fat mass accumulation and increases fat oxidation in humans (Han et al, 2018;Kimura et al, 2017;Yamaguchi et al, 2019).…”