Artificial Sweeteners

Preceptor: Erin Arra, MS, RD, LD

Intern: Mike Daniels
Date: 1/15/16

Background - 1958 Food Additives

Amendment1
* FDA Regulation: 1958 Food Additives
Amendment to the Federal Food, Drug,
and Cosmetic Act
* Required all food additives to undergo
premarket approval

* Probable Intake, cumulative effect,

and toxicological data used to
determine safety.
* Toxicology studies look at
absorption, distribution, metabolic
pathways, elimination
* Highest No Effect Level (HNEL)
* Acceptable Daily Intake (ADI)
Usually a 100-fold safety factor
* Safe amount that can be consumed
every day without adverse effects.

Figure 1. 1958 Food Additives Amendment

* Estimated Daily Intake (EDI)

Assumes that product will replace all
other sweeteners.

FDA-Approved Artificial NNS2-3

NNS

Times Sweeter than

Sucrose

ADI and EDI

# of Sweetener Packets
to reach ADI for 60 kg
(132#) person

Acesulfame Potassium
(Ace K)

200X

ADI: 15 mg/kg BW
EDI: 0.2-1.7 mg/kg BW

23

Aspartame

160-220X

ADI: 50 mg/kg BW
EDI: 0.2-4.1 mg/kg BW

75

Neotame

7,000-13,000X

ADI: 18 mg/kg BW
EDI: 0.05-0.17 mg/kg BW

23

Saccharin

300X

ADI: 5 mg/kg BW
EDI: 0.1-2 mg/kg BW

45

Sucralose

600X

ADI: 5 mg/kg BW
EDI: 0.1-2 mg/kg BW

23

Advantame

37,000X!

EDI: 1.2 mg 3 mg

4,920

NNS US Trends4

Editorial Article For Providers5

*What does this mean for the consumer? It means that

LCSs seem to be doing exactly what they were designed to
do: helping reduce total energy intake while providing the
sweet taste we value. This is good news for people trying
to lose or to not gain weight.
*You can confidently use this tool (LCSs) without worrying
that you might be unintentionally hurting your weightmanagement efforts.
*The author has received grant funding from the American
Beverage Association and from the Coca Cola Company. He
has served as a consultant for the following companies: the
Coca Cola Company, General Mills, and McDonalds.

Snapshot Cancer6-7
* Cancer 2015 systematic review human studies only Current data do not show
any association between artificial sweeteners and kidney, brain, GI, and breast
cancer.
* 2012 article combined 2 cohort studies (Nurses Health Study and the Health
Professionals Follow-Up Study), covering 22 years.
* Found that only men consuming 1 diet soda (aspartame) per day were at an increased risk
of non-Hodgkin lymphoma (RR: 1.31) and multiple myeloma (RR: 2.02)
* Mean intakes of aspartame for NHS was 102 mg/d in 2002 and 114 mg/d in HPFS
* Authors concluded that gender differences signify that results should be interpreted with
caution unable to rule out chance.
* More research is needed.
* Theoretical Concern (EAL): Aspartame is a methyl ester of the dipeptide of phenylalanine
and aspartic acid.
* Broken down into methanol, which Is metabolized to formaldehyde and formic acid. (very small
amount)
* 4-6 x more methanol in a serving of tomato juice
* Studies have shown that adults consuming up to 200 mg/kg BW (50 times the EDI) did not increase
formic acid in the blood, however small increases in methanol were seen.

Snapshot Type 2 DM6

*2015 systematic review 7 cohort studies 4 studies (9-24
years) of good quality indicated no relationship between
artificial sweeteners and risk of T2DM, whereas 3 showed a
positive association.
*Problems with cohorts:
*1. **Reverse Causality** - Those at higher risk choose artificiallysweetened beverages.
*2. FFQ typically only performed at baseline Change over time

Snapshot Weight (Youth)8

Snapshot Weight (Adult)8

Interesting Studies9
*2013 randomized crossover study (n=17) that looked at
ingestion of sucralose (48 mg) or water followed by ingestion
of 75 grams of glucose.
*Findings: Sucralose caused significantly greater peak glucose
concentrations, greater peak insulin, and decreased insulin clearance
rate.
*Key Points:
*Highlighted distinction between chronic NNS users and those that never
use NNS Different effects?
*Only in obese participants
*Calls into question whether sucralose is physiologically inert

Interesting Studies Cont.10

* 2014 animal study (mouse) and
human study that essentially
looked at effects of saccharin on
glucose tolerance.
* 1. Demonstrated in mice that
saccharin altered gut microbiota,
inducing glucose intolerance.
* 2. Looked at ongoing cohort
study and found that regular
consumers of NNS had intestinal
microbial differences.
* 3. Seven healthy volunteers who
dont consumer NNS were given
saccharin (MAX ADI).
* 4/7 developed significantly
worse glycemic responses 5-7
days after responders.
* Gut bacteria from responders
were transferred to germ-free
mice, which subsequently
induced glucose intolerance.

Figure 2. Study Workflow

Potential Mechanisms + Current

Issues9-10
* 1. Compensatory consumption
* 2. Altered gut microbiota
* 3. Cephalic phase stimulation NNS potentially could stimulate gastric secretions
and hunger.
* 4. Novel gut sweet taste receptors human studies thus far indicate that NNS are
insufficient to elicit incretin response.
* Incretins hormones secreted by GI neuroendocrine cells that enhance glucosestimulated insulin secretion. Example is GLP-1 , hence GLP-1 agonists.

* Current Issues:
* Overall lack of human RCTs
* Cohort data hard to generalize and compromised.
* Small sample size, type and amount of NNS, never-user vs. chronic, gut microbiota, BMI
* Industry-funded studies
* With DGAs 2015-2020 focus on added sugars greater intake of NNS?

References
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1. USC. Federal Food, Drug, Cosmetic Act. 2011;(3055):1-6.

2. Fitch C, Keim KS. Position of the Academy of Nutrition and
Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr
Diet. 2012;112(5):739-758. doi:10.1016/j.jand.2012.03.009.
3. Otabe a, Fujieda T, Masuyama T, Ubukata K, Lee C. Advantame-an overview of the toxicity data. Food Chem Toxicol. 2011;49 Suppl
1:S2-S7. doi:10.1016/j.fct.2011.06.046.
4. Mattes RD, Popkin BM. Nonnutritive sweetener consumption in
humans: Effects on appetite and food intake and their putative
mechanisms. Am J Clin Nutr. 2009;89:1-14.
doi:10.3945/ajcn.2008.26792.
5. Hill JO. What do you say when your patients ask whether lowcalorie sweeteners help with weight management? 1 3. 2014:739740. doi:10.3945/ajcn.114.094466.1.
6. Olivier B, Serge AH, Catherine A, et al. Review of the nutritional
benefits and risks related to intense sweeteners. Arch Public Heal.
2015;73(1):41. doi:10.1186/s13690-015-0092-x.
7. EAL
8. Pereira M a. Sugar-Sweetened and Arti fi cially-Sweetened
Beverages in Relation to Obesity Risk 1 3. 2014;2006:797-808.
doi:10.3945/an.114.007062.evidence.
9. Pepino M. Sucralose Affects Glycemic and Hormonal Responses
to an Oral Glucose Load. Diabetes Care. 2013;36(October 2012).
doi:10.2337/dc12-2221.
10. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce
glucose intolerance by altering the gut microbiota. Nature.
2014;514(7521):181-186. doi:10.1038/nature13793.