You may have heard the expression
“knowledge is power.”
Well, today we’re going to give you more power
to control your diet and lifestyle
by giving you the facts.
Welcome to the Nutrition Facts Podcast.
I’m your host, Dr. Michael Greger.
Today we look at the safety
of fourth generation sweeteners
such as the rare sugar allulose.
First there was sugar and high fructose corn syrup,
the original industrial sweeteners.
They were cheap, but had lots of empty calories,
and contributed to diseases
such as obesity, type 2 diabetes, cavities, and metabolic syndrome.
So then came the second-generation sweeteners, the artificial sweeteners,
the colored pastel packets: Nutrasweet, Splenda,
Sweet & Low. Practically zero calories,
but adverse effects have been described, cautions have been raised.
For example, artificial sweeteners were found to induce glucose intolerance
by altering the gut microbiome, thereby producing
the counterintuitive effect of inducing metabolic derangements.
They also taste kind of funny.
Enter the third-generation Sweeteners, sugar alcohols,
such as sorbitol, xylitol, and erythritol, low-calorie sweeteners,
however, their laxative effects can create difficulties,
which brings us to rare sugars like allulose, which are
natural sweeteners with low or zero calories and a sugar-like taste.
For those of you who haven't heard of allulose,
it's been through a bit of rebranding.
Just like rapeseed oil morphed into canola, forcing municipalities
to update their town slogans,
allulose used to be called psicose, a sugar you may not want to eat
in the shower.
The name "psicose" is derived from the antibiotic from which
it was isolated --- a strange origin story for a sweetener.
In the Frontiers of Bioengineering and Biotechnology, emphasis
is placed on the fact that allulose is a real and natural sugar
rather than artificial, but ironically if you look at a reference they cite,
it talks about how allulose is made, via functionalized
polyhydroxyalkanoate nano-beads
decorated with D-tagatose 3-epimerase (DTE)
produced in recombinant endotoxin-free branded bacteria.
And now technically allulose is a natural sugar, a so-called rare sugar,
which have been defined by the International Society of Rare Sugars
as sugars that are present in limited quantities in nature.
But recent technological advances, such as enzymatic engineering
using genetically modified microorganisms, now allow
manufacturers to produce otherwise rare sugars
like allulose in substantial quantities.
But small amounts have pre-existed in the food supply,
so the FDA granted it generally recognized as safe status,
but it's been like really small amounts, like a few
dozen milligrams, or a quarter of a quarter of a quarter of a teaspoon.
See, allulose is generated when fructose is heated.
And allulose is created incidentally
in the process by which high fructose corn syrup is made.
So basing the safety of allulose on the fact that it's already been
present in the food supply isn't very convincing.
You don't know if it's safe until you put it to the test.
Unlike table sugar, allulose is safe for the teeth;
isn't apparently metabolized by cavity-causing bacteria
to make acid and build up plaque.
It doesn't raise blood sugars, even in diabetics.
It can be labeled as having zero calories, though technically
it may have like one and a half calories per teaspoon,
similar to what you see with erythritol.
Also like erythritol, it's only about 70% as sweet as table sugar
but has almost the same taste, performance,
and texture as regular sugar.
Are there any toxicities?
Allulose is considered a relatively nontoxic sugar.
What does that mean?
Well, in pets, we know a sweetener called xylitol can
be extremely dangerous to dogs.
As little as a half teaspoon in a 30-pound dog can be life-threatening,
whereas a similar dose of allulose apparently wouldn't be a problem,
though like over half cup at a time could make them sick.
This was a single dose study though.
The long-term safety of allulose was tested over a period
of a few months and didn't seem to cause any harmful effects at a dose
of about one and a half teaspoons a day for healthy 30-pound dogs.
In fact, their cholesterol actually went down,
leading the investigators to suggest clinical studies to see
if it's something vets should start prescribing for overweight pooches.
What about in people?
When the dose of allulose was gradually increased
to identify the maximum single dose for occasional ingestion,
no cases of severe gastrointestinal symptoms were noted
until a dose of 0.4 g/kg of bodyweight was reached,
which could be about 7 teaspoons, with severe symptoms
of diarrhea noted once you get up around 9 teaspoons.
And you say, "who could eat that much sugar at a time anyway?"
A single can of Coke has 10 teaspoons,
and a bottle of Mountain Dew has nearly twice that.
So allulose is clearly not suitable as a standalone sweetener
for sugary beverages.
In terms of the daily upper limit given in smaller doses
throughout the day, once you hit around 17 teaspoons a day,
depending on your weight, people start getting
severe nausea, abdominal pain, headache, diarrhea.
So people should probably stay under single doses
of about 7 teaspoons,
and not exceed around 15 for the whole day.
The average American may be getting 17 teaspoons
of added sugar a day, so it's certainly not something
the food industry can completely switch over to.
In this way, allulose is close to xylitol in terms of
maximal single dose,
whereas the average-weight man in the US could get away with
14 teaspoons of erythritol at a time,
and the average woman, 15 teaspoons.
Still not enough to sweeten a bottle of Coke, but offers
a little more leeway for sweetening tea
or sprinkling on a grapefruit or something.
Allulose is claimed to provide health benefits
though, compared to erythritol.
Forth generation sweeteners like allulose are said to have
as an advantage: additional functions.
We'll find out if that's true, next.
Allulose is a kind of low-calorie sugar naturally existing
in very small quantities,
but now industrially produced as a commercial sweetener,
said to have advantages
that make it comparable to erythritol as a sugar substitute.
It's said to have anti-diabetic effects,
but this was in obese mice.
Allulose decreases LDL cholesterol levels in high fat-fed hamsters and
is said to have a substantial impact on obesity in lard-munching mice,
but what about men and women?
In a petri dish, allulose inhibits fat cell precursors
from maturing into fat cells
and reduced the amount of fat accumulation within fat cells.
Therefore, the researchers conclude, allulose may be
a promising sugar substitute for an anti-obesity diet,
but you don't know until you put it to the test.
They gave people about a teaspoon of allulose a half hour
before eating a meal, and compared to the no-sugar control group,
the allulose group started burning more fat.
The researchers concluded that allulose enhances
after-a-meal fat burning, indicating that it could be
a novel sweetener to control and maintain
healthy body weight through enhanced energy metabolism.
Okay, but first of all, it was only 15 calories of fat
burned over that 4-hour period.
And they didn't burn more calories overall.
They just switched from burning carb calories to fat calories
and so may have just switched back later on and made up
for it later in the day. You can't just look at one meal.
You need to track people's actual weight over time, and here we go.
A weight reducing effect of a syrup that included about 5% allulose,
compared to high fructose corn syrup.
The results show significant decreases in body weight, body fat,
and waist circumference, but it was some proprietary syrup mixture,
and look, anything would look good against high fructose corn syrup.
This is the study I've been looking for.
Evaluating the effect of allulose for fat mass reduction in humans.
Over a hundred individuals
randomized to a placebo control -- sucralose --
or a teaspoon of allulose twice a day,
or one-and-three-quarter teaspoons twice a day,
and despite no change of physical activity
or calorie consumption between the two groups,
body fat was significantly decreased following allulose supplementation.
They even took CT scans, so they could tell where
the fat was disappearing from.
Now, the drop in body fat was only about 2 pounds over 12 weeks,
and the drop in abdominal fat in the higher dose group
was almost totally a drop in subcutaneous fat,
the flabby superficial fat, not the dangerous visceral fat
deeper down that really matters for health.
But still, a body fat loss despite no change in calorie intake,
similar to what was seen in the mice,
but the hamster effect did not materialize:
no significant change in LDL cholesterol in either
of the allulose groups.
What about the purported anti-diabetes effects?
If you have people chug a beverage with up to about 2 teaspoons
of allulose alone -- previously known as psicose -- or with
a big load of rapidly-digesting carbs, the allulose alone has predictably
no influence on blood glucose or insulin concentration.
Yet when you consume allulose along with the refined carbs,
there is actually a suppression of the elevation of blood sugar and insulin,
and by a significant amount: a 30% drop in blood sugar and insulin levels
over a two-hour period. We think it's because the presence of allulose
impairs the absorption of sugar through the intestinal lining,
because they all might be competing for the same sugar transporter.
Yeah, but who's chugging maltodextrin? What about just like a regular meal?
And here we go -- and in borderline diabetics
who could use some blood sugar spike suppression.
A randomized double-blind placebo- controlled crossover experiment
to see what drinking one and a quarter teaspoon of allulose
in a cup of tea with a meal would do,
and indeed a significant drop, though only about 15%.
You can see how they tried to exaggerate the y-axis.
They also did a second experiment: randomized people to a little over
a teaspoon of allulose three times a day with meals for 12 weeks.
Nice to see there didn't appear to be any adverse side effects,
but they also didn't find any weight loss effects,
in contrast with that other study.
So the body fat data [are] mixed and so too [are] the sugar data.
This study found no effects of allulose on blood sugars
in healthy participants, though a similar study on diabetics did.
A systematic review and meta-analysis of all such controlled feeding trials
suggest that the acute benefits on blood sugars
was of borderline significance,
and it's unclear whether or not this alone could translate
into meaningful improvements in blood sugar control over time,
so maybe it's not enough to just add allulose.
You might actually have to also cut out the junk.
Although ability to suppress blood sugar responses
is the most well studied aspect of allulose, I do just want
to cover one last angle: the fact that allulose extends
the lifespan of a tiny roundworm called "C. elegans" through
a dietary restriction mechanism, even though they ate
the same amount of food.
Two months in, just a few percent of the control group were still alive,
whereas twice as many in the low allulose group
and about 25% still around in the higher allulose group.
We think it worked boosting the expression and activities
of antioxidant enzymes in the body,
extending lifespan by mopping up free radicals.
But who cares about the survival curves of worms?
Well, C. elegans is a well-studied model of aging and longevity,
but mostly just for convenience sake,
but does share most of the longevity genes or pathways we're interested in.
It would be nice to see experiments on at least human cells, and here we go.
The effect of allulose on free radicals and oxidative stress
in human coronary artery endothelial cells --
the cells that line the inside of our arteries.
Add a bunch of sugar, and free radical levels shoot up,
but add the same amount of sugar along with some allulose,
and it's as if you never even added the sugar,
and this then translates to inhibiting the expression
of an inflammatory marker
that plays a role in the buildup of atherosclerotic plaque.
However, it's still too early to draw conclusions
about the clinical relevance of these data. To conclude,
are these rare sugars like allulose healthy alternatives
for traditional sweeteners? Well, considering the variety
of potentially beneficial effects of allulose
without known disadvantages from metabolic and toxicological studies,
allulose may currently be the most promising rare sugar,
but how much is that saying?
We just don't have a lot of good human data.
As a result of the absence of these studies,
it may be too early to recommend rare sugars for human consumption.
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