Interesting: D-Allulose Promotes Fat Loss - Not Compared to Sugar, but Compared to Non-Caloric Sweeteners

The reduction in belly fat was significant - in the absence of dieting and compared to another zero-calorie sweetener, that is.
D-Allulose is one of those purported weight loss agents with an impressive research record from rodent studies. Now, a recent human trial suggests: it may work in overweight men and women, too.

With it being one of the newer sugar substitutes, you may not be familiar with d-allulose (also called d-psicose). So, here's the gist: It's the C-3 epimer of d-fructose, has (only) 70% of the sweetness of sucrose and ZERO calories (well, almost) ... ah, and did I say that it's rarely found in nature.
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That doesn't mean its the invention of a mad scientist, though, it is in fact present in small quantities in commercial mixtures of d-glucose and d-fructose obtained from the hydrolysis of sucrose or isomerization of d-glucose. Large scare production requires enzymatic treatment of d-glucose and has recently become available at reasonable prices. As Han et al. (2018), the authors of the previously hinted at paper point out,

"d-allulose is generally recognized as safe (GRAS), according to the United States department of agriculture (USDA) regulations" (Han 2018).

Aside from its beneficial effects on lipid metabolism (Matsuo 2001Ochiai 2014; Han 2016), the existing rodent data suggests that it will also enhance glucose uptake from the liver and suppresses hepatic lipogenic enzyme activities (Nagata 2015). In addition, it lowered food intake while it increased energy expenditure during darkness and soleus muscle lipoprotein lipase activity in rats pair-fed the high-sucrose diet (Ochiai 2014). And as if that wasn't enough, yet, the same rodent studies also suggest that "d-allulose inhibits dietary fat absorption in the small intestine and increases β-oxidation in fat tissue under pair-feeding conditions in mice fed with a high-fat diet" (Han 2018) - No wonder that "[m]ost studies indicate that d-allulose induces a decrease in body weight, fat mass, and food or energy intake (ibid).
Would be nice to see the preliminary research on d-allulose's use as a sugar substitute in foods being independently confirmed + extended to other foods like pancakes or protein bars.
Did you know? While the study at hand didn't show any effects on inflammation, this would probably have changed if the control treatment was regular sugar. After all, the replacement of only 20% of the sugar in sponge cake with d-allulose produced a significant increase in the antioxidant properties of a cake that was also softer and got rid of the eggs-odor some people hate... ah, and did I mention that d-allulose has also been used in soy milk based, drinkable yogurt, where it reduced the acidity, increased the viscosity and made the fake-yogurt taste significantly milder without affecting potentially health-improving bioactive bacteria?
With the lack of adequately powered human studies (often using placebos that were anything but neutral wrt their metabolic effects, like sugar or fructose) to confirm the relevance of the existing rodent data, however, it has hitherto been really premature to recommend supplementation, let alone the large-scale incorporation of d-allulose as a sugar-replacement in processed foods.

How much d-allulose does it take to get jacked? 

This, or rather something like this is the research question of Han's "preliminary study". An RCT designed to answer the important dosage question to inform the methodological design of an upcoming main study, which would be performed using dual-energy X-ray absorptiometry (DEXA) equipment for body fat measurement.

What? Yeah, you read that right. The study at hand didn't use the gold-standard of body composition measurement. It was conducted in 121 Korean subjects (aged 20–40 years, body mass index ≥ 23 kg/m²; not jacked, but not sick and/or completely metabolically deranged, either) who consumed either
  • placebo control (sucralose, 0.012 g × 2 times/day), 
  • low d-allulose (d-allulose, 4 g × 2 times/day), or
  • high d-allulose (d-allulose, 7 g × 2 times/day) 
over the course of 12 weeks... and even though the authors didn't use DXA scan, the body composition data was gathered by the means of a decent hand + feet based impedance analyzer (see the model).
Is that the "new" sweetener in Quest Bars? Usually, I don't mention specific products, but since I got the first questions about that 2 minutes after posting this, here's your answer: yes, it is!
Moreover, Han et al. tracked their subjects' nutrient intake and got computer tomography (CT) scans to assess changes in subcutaneous and abdominal body fat (interestingly visceral fat was decreased only non-significantly), as well as blood draws to assess their subjects' before and after plasma lipid profiles.
Figure 1: Changes in body composition in response to 2x4g and 2x7g of d-allulose per day for 12 weeks (Han 2018).
Ok, the results (see Figure 1) were not earth-shattering. Keep in mind, though, the weight and body fat loss occurred in the absence of any deliberate dietary changes/energy restriction, as the subjects "were [simply] instructed to maintain their routine food intake and physical activity, and consume two bottles of supplements per day" (Han 2018).

No dieting, but still significant fat loss? Too good to be true!?

Considering the fact that the placebo was an inert no-calorie sweetener (not sugar or fructose as in some other studies), the statistically significant beneficial effects on body weight, BMI, body fat percentage and total body fat are newsworthy - also because the CT scans confirm that the subjects lost both abdominal and subcutaneous fat compared to the placebo group; and all that in the absence of significant differences in nutrient intakes.

What the scientists did not observe, however, were the previously reported improvements in plasma lipid profiles, markers of liver and kidney function, and/or changes in major inflammation markers among groups. With the beneficial effects on body composition being increased with increasing dosages of d-allulose, it would be premature to discard the possibility of directly health-relevant effects of this rare sugar altogether.
Don't dare to tell me 'skippin' sucralose did the trick' | check your science!
Bottom line: 4g twice a day is not necessarily something you'd want to consume as a supplement in pill form.

With d-allulose being regarded as a generally recognized safe (GRAS) food ingredient and continuously plummeting production costs, this stuff could, however, be of interest for the food industry - as a (potentially more effective) alternative to currently used no-calorie sweeteners such as sucralose, the placebo supplement from the study at hand.

Follow up research warranted: In addition to the use of DXA-scans, future studies should also investigate the mechanism by which d-allulose works its fat-loss-magic. As of now, it seems to be unrelated to any of the usual suspects, i.e. reduced inflammation, improved insulin sensitivity, augmented fatty acid oxidation, or appetite/food intake. Based on the rodent evidence we have (Han 2016), the most likely mechanism is the suppression of dietary fat absorption via regulation of respective genes in the small intestine and subsequent increases in fecal lipid contents. If that's also what helped the human subjects in the high-dose group of the study at hand shed -21.31 ± 30.45 cm², i.e. 6.4%, of their belly fat and -20.59 ± 24.80 cm², i.e. 9%, of their subcutaneous fat in the absence of conscious dieting isn't clear... the same goes for the general efficacy of the treatment - after all, the standard deviations within the group were huge. Plus: The claim that it's zero calories must be doubted based on observations Lida et al. made in 2010 - they estimate the actual caloric value to be < 1.6 kJ/g, ok 0,38kcal/g is still low, but technically, it is not ZERO (note: d-allulose is the same molecule as d-psicose - just different names to refer to it) | Comment on Facebook!
  • Han, Youngji, et al. "d‐Allulose supplementation normalized the body weight and fat‐pad mass in diet‐induced obese mice via the regulation of lipid metabolism under isocaloric fed condition." Molecular nutrition & food research 60.7 (2016): 1695-1706.
  • Han, Youngji, et al. "A Preliminary Study for Evaluating the Dose-Dependent Effect of d-Allulose for Fat Mass Reduction in Adult Humans: A Randomized, Double-Blind, Placebo-Controlled Trial." Nutrients 10.2 (2018): 160.
  • Iida, Tetsuo, et al. "Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans." Metabolism-Clinical and Experimental 59.2 (2010): 206-214.
  • Matsuo, Tatsuhiro, et al. "Dietary D‐psicose, a C‐3 epimer of D‐fructose, suppresses the activity of hepatic lipogenic enzymes in rats." Asia Pacific journal of clinical nutrition 10.3 (2001): 233-237.
  • Nagata, Yasuo, et al. "d-Psicose, an epimer of d-fructose, favorably alters lipid metabolism in Sprague–Dawley rats." Journal of agricultural and food chemistry 63.12 (2015): 3168-3176.
  • Ochiai, Masaru, et al. "D-Psicose increases energy expenditure and decreases body fat accumulation in rats fed a high-sucrose diet." International journal of food sciences and nutrition 65.2 (2014): 245-250.
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