Upload
others
View
1
Download
0
Embed Size (px)
Citation preview
Artificial Sweeteners: A Bitter Aftertaste?
Edwin Cox, M.D.OLLI
Basic concepts of NASNAS = Non-nutritive artificial sweeteners or non-caloric artificial sweeteners• AKA “high-intensity sweeteners”
NAS are substances that stimulate sweet receptors in the tongue, providing the pleasurable sensation of sweetness, but do not enter human metabolism directly
NAS are more potent than sugars, thus provide sweetness at lower amount• Exception: poly-alcohols (sorbitol, glycerol, xylitol) have about same
sweetness as sugar but do not raise blood glucose (not absorbed or not metabolically active)
Basic concepts of NAS (cont’d)NAS generally are not absorbed in GI tract and were thought to pass out unchanged in the stool• Those that are absorbed are metabolically inactive• Spoiler alert: We now know that intestinal bacteria metabolize several NAS
and produce active byproducts
NAS that are approved (i.e., FDA) have been tested and not found to cause untoward effects in lab animals or humans • Several are banned due to adverse effects; others were banned temporarily
but reauthorized (e.g., saccharin)• Spoiler alert: New areas of testing give rise to substantial concerns regarding
safety of several NAS that have not been incorporated into official advice
Artificial sweeteners
Popular NAS
Aspartame (left), sucralose (above), saccharin
“Accepted” uses of NAS“Accepted” is in quotes to indicate that these uses are currently under scrutiny due to evidence to be considered here
Prevention & control of diabetes• As an alternative to sugars, would be expected to avoid raising blood glucose
Prevention & reversal of obesity• As an alternative to sugars, would be expected to avoid adding caloric
content to diet
Prevention of dental caries
Prevention of reactive hypoglycemia
Sweetness at lower product cost
FDA guidance on NAS safetyAre high-intensity sweeteners safe to eat?
“Based on the available scientific evidence, the agency has concluded that the high-intensity sweeteners approved by FDA are safe for the general population under certain conditions of use. For certain highly-purified steviol glycosides and extracts obtained from monk fruit, FDA has not questioned the notifiers’ GRAS determinations under the intended conditions of use described in the GRAS notices submitted to FDA.”
GRAS = Generally recognized as safe
May, 2014https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm397716.htm
Medical guidance on NASAmerican Diabetes Association, American Heart Association, etc, are generally affirming of the uses just mentioned
ADA• “The evidence reviewed suggests that when used judiciously, [NAS] could
facilitate reductions in added sugars intake, thereby resulting in decreased total energy and weight loss/weight control, and promoting beneficial effects on related metabolic parameters.” August 2012
AHA• “Foods and beverages that contain [NAS] can be included in a healthy diet, as
long as the calories they save you are not added back by adding more foods as a reward later in the day, adding back calories that take you over your daily limit.” April 2018
Quick review of glucose digestion
Ingested glucose winds its way to the small intestine, where it is absorbed into the intestinal lining cell by a special transporter molecule, SGLT1, in the lumen-facing cell membrane
Glucose proceeds onward into the blood at the basal cell membrane by transporter GLUT2
Blood glucose rises as glucose is absorbed
Pancreas: crucial digestive organNestled in the duodenum (first part of small intestine)
Secretes digestive enzymes amylase, lipase and protease into the duodenum (exocrine gland)
Secretes insulin and glucagon into the blood from islands of tissue studded within pancreas (endocrine gland)
Rising Glucose Insulin release→
Blood passes through pancreas
Islets within the pancreas contain specialized cells for regulating glucose
Rising glucose level stimulates insulin secretion from pancreatic islet beta cells into the blood
Glucose and insulinInsulin is the master control molecule to regulate blood glucose level
Polypeptide (i.e., protein) of 51 amino acids in its monomer active form
Diagram shows storage hexamer (six units) form; greater stability
Monomer secreted by pancreas islet cells in response to rising glucose
Signals liver, muscles and fat cells to remove glucose from blood
Insulin effect on fat and muscleInsulin binds to insulin receptor on liver, fat and muscle cells
Activates glucose transporter to promote glucose uptake
Removing glucose from blood lowers glucose level
Glucose is converted into glycogen for storage in liver
Glucose is converted into fatty acid for storage in fat cells
Glucose is used as the energy supply in muscle and brain
glucosetransporter-4 insulin
receptor
6glycogen 4
3
pyruvate
fatty acids
glucose
Blood glucose following a mealNormal individual has a modest increase in blood glucose, peaking about one hour and returning to normal in two to three hours
Insulin secretion closely matches glucose absorption, driving glucose into fat and muscle cells, thereby keeping glucose level nearly constant
HyperglycemiaRefers to blood glucose levels that rise substantially above those in healthy individuals after a meal, or remain elevated after digestion is complete
Hyperglycemia is the defining characteristic of diabetes mellitus and prediabetes
Hyperglycemia
Hyperglycemia may occur because the pancreas is not secreting enough insulin relative to the glucose level (type 1 diabetes mellitus, advanced T2DM)
Alternatively hyperglycemia may occur because the cells that remove glucose from the blood are not responding to the insulin signal “insulin →resistance” (metabolic syndrome, early T2DM)
Glucose metabolism testingGlucose metabolism is tested by the GTT (glucose tolerance test)
Glucose intolerance is when, after consuming glucose, blood glucose rises too high or/and is elevated for too long
Glucose intolerance indicates either:• Insufficient insulin secretion by pancreas relative to amount of
glucose consumed• Insulin resistance, that is, fat and muscle do not respond to
insulin
Glucose tolerance testOral dose of glucose consumed (50 g)
Blood glucose sampled at intervals
Normal: Slight [1 MIN] to moderate [1 MAX] rise in blood glucose peaking at 60-80 min, falling back to baseline
Prediabetes [2]: Rises higher, falls back more slowly
Diabetes with hypoglycemia [4]: Rises higher, falls below normal later
Poorly controlled diabetes [3]: Elevated baseline glucose, rises even higher with glucose ingestion
So, what’s the problem with NAS?
Nature 2014
Mice given NAS develop glucose intolerance
Mice fed saccharin (Sweet’N Low), sucralose (Splenda) or aspartame (Equal)
NAS added to glucose-containing drinking water
NAS accompanied regular chow
Glucose tolerance curves at 11 weeks of consuming any of the three NAS showed marked glucose intolerance compared to glucose-only controls
Glucose intolerance of NAS in mice depends on gut microbes
Mouse microbiome is markedly altered
Balance in abundance of various species is changed
Production of short chain fatty acids by bacteria is changed• More acetate, propionate, less butyrate
Metabolic signaling and energy harvest is changed, upsetting glucose metabolism and energy balance
These changes can be prevented by antibiotic suppression of bacterial growth
Glucose intolerance transmissible to germ-free mice
Stool from mice rendered glucose intolerant by NAS were transferred to germ-free mice
Recipient mice became glucose intolerant
Glucose intolerance in recipient mice was prevented by giving antibiotics
Therefore glucose intolerance was transmitted with the bacterial transfer
Human high-NAS consumersNon-diabetic subjects of a clinical nutrition study
NAS intake determined from food-frequency questionaire• 40 high-NAS consumers• 236 non-consumers
Blood work taken from subjects included HbA1c, a measure of average blood glucose over preceding 3 months
High-NAS consumers had higher HbA1c (p<0.002)
Was high HbA1c the result of high-NAS consumtion, or the other way around, or neither?
Human subjects given NAS
7 healthy volunteers• Age 28-37, 5 M & 2 F, NAS non-consumers
All given saccharin 120 mg 3 times a day• FDA Acceptable Daily Intake• Daily for seven days
Glucose tolerance test administered daily
Non-responders to NAS
Three subjects had GTT after 5-7 days of saccharin not different from GTT in days 1-4
NAS responders
Four subjects had markedly altered GTT after 5-7 days of saccharin intake
NAS responders vs non-responders
Glucose response area-under-curve (AUC) more than doubled in four responders (R1, R2, R3, R4) after 5-7 days of saccharin
Gut microbiome vs NAS responseNAS responders had distinct bacterial species distribution compared to non-responders
That is, specific species are responsible for the transition to glucose intolerance
Glucose intolerance transmissible from human to mice
Stool transplanted from a human NAS responder to germ-free mice caused those mice to be glucose intolerant
What does it all mean?
NAS are not just metabolically inert compounds that taste sweet and pass on through with no consequences
NAS can suppress desirable bacteria, promote growth of less desirable ones
The promoted bacteria have effects on our metabolism, such as glucose intolerance and weight gain
The authors conclusion
“Our findings suggest that NAS may have directly contributed to enhancing the exact epidemic that they themselves were intended to fight.”
It is entirely possible that NAS used habitually may cause the very complications – diabetes, weight gain – that they are intended to prevent!
My conclusions about NASThese findings regarding effects of NAS in mice and humans should be considered preliminary until confirmed in other labs and other subjects
Nevertheless, sweeteners provide no nutritional value and possibly encourage consumption of other undesirable foods due to their “taste appeal”
It’s conceivable – thought unproven – that it’s as safe to consume modest amounts of sugar to satisfy our sweet tooth rather than use NAS
RecommendationsMinimize your consumption of all sweeteners – sugar (in its many forms) and NAS• Wean off the addiction to sweet foods and beverages
That includes steering clear of manufactured foods containing NAS• “Sugar-free” does not mean healthy
If you are having success in achieving specific goals by using NAS, don’t abandon them – yet• Weight maintenance, diabetic control, for example
Stay informed of further developments