BMJ: Artificial sweetener safety adds new concerns! Studies of more than 100,000 people have found that high total sweetener intake in the diet is associated with a 9% and 18% increased risk of cardiovascular disease and cerebrovascular disease

*For medical professionals only

Although sugar is "happy", you can't eat
too much.
The World Health Organization recommends that the energy obtained from free sugars should not exceed 5% of the daily dietary energy intake [1].

It has become a consensus that
excessive sugar intake can cause adverse effects on human health.

In order to reduce the amount of sugar used while maintaining the sweet taste, artificial sweeteners have emerged as a substitute for sugar, but some studies in recent years have shown that artificial sweeteners may not be as healthy and harmless
as we think.

Recently, Charlotte Debras and her research team at the Sorbonne Norte in Paris published important research results in the British Medical Journal [2].

In a prospective cohort study of more than 100,000 people, they found that high total dietary intake of artificial sweeteners was associated
with a 9% increased risk of cardiovascular disease and an 18% increased risk of cerebrovascular disease.
Among the artificial sweeteners covered in the study, aspartame was associated with a 17% increased risk of cerebrovascular events, while acesulfame potassium and sucralose were associated
with a 40% and 31% increased risk of coronary heart disease.

These findings provide an important reference for re-evaluating the use of artificial sweeteners and suggest that artificial sweeteners may be a risk factor for
cardiovascular disease.

Screenshot of the front page of the paper

Artificial sweeteners have a huge global market of $7.
2 billion and are growing at a rate of 5% per year[3].

Common artificial sweeteners include acesulfame potassium, aspartame and sucralose
.

Cardiovascular disease is the leading cause
of death worldwide.
Many previous studies have found that the use of artificial sweeteners is associated with the development of risk factors for cardiovascular disease, such as weight changes, high blood pressure, inflammation, vascular dysfunction, and intestinal flora disorders
.

Previous NutriNet-Santé cohort studies and meta-analyses have shown that high intake of beverages containing artificial sweeteners is associated with increased cardiovascular mortality [4], but beverages represent only a partial source of artificial sweeteners, and observing the total intake of artificial sweeteners in the diet may be more beneficial to reveal the link
between it and the risk of cardiovascular disease.
To that end, Charlotte and her colleagues conducted research
.

The study, also based on the NutriNet-Santé cohort study, launched in May 2009, recruited 103388 volunteers with an average age of 42.
2 years, 79.
8% of whom were women, and had a median follow-up of 9 years
from 2009 to 2021.

The volunteers for the study, aged ≥ 18, signed up online and then filled out questionnaires online about diet, health, lifestyle
, etc.
Non-consecutive 3 days were randomly selected for 24-hour diet recording
over a two-week period.
Eating records include photos and quantities
of all foods and drinks ingested throughout the day.
Dietary assessment is validated
by conversations with dietitians and markers of hematuria.

Artificial sweetener intake is assessed
through an interactive online food recording tool.
In addition, volunteers can report their health
status through questionnaires and websites during follow-up.
The researchers collected medical records
of volunteers at the time of cardiovascular disease.
Finally, the relationship between artificial sweeteners and the risk of cardiovascular disease was evaluated
by a multiplex-corrected Cox risk model.

In this study, a total of 37.
1% of participants consumed artificial sweeteners
.
The average intake of artificial sweeteners for all participants was 15.
76 mg/day, while the average intake of artificial sweeteners was 42.
46 mg/day, equivalent to 100 mL of sugar-free beverages
.
According to the median sex, the volunteers were divided into three groups: non-intake (n=65028), low intake (n=19221), and high intake (n=19139), with cut-off values of low and high (16.
44 mg/day (male) and 18.
46 mg/day (female),
respectively.
The average intake in the low-intake group was 7.
46 mg/day, while the average intake in the high-intake group was 77.
62 mg/day
.

Through dietary analysis, aspartame, acesulfame potassium and sucralose contributed the highest to the total amount of artificial sweeteners, at 57.
9%, 29.
2% and 10.
1%,
respectively.

The contribution of different types of artificial sweeteners to total intake

Sugar-free beverages accounted for the largest "contribution" to the total amount of artificial sweeteners, accounting for 52.
5%, followed by tabletop sweeteners, in the form of tablets, liquids or powders, added by participants themselves to yogurt, hot drinks or cooked foods at 30.
2%.

Other sources of artificial sweeteners include yogurt, dry cheese, and beverages with both added sugar and artificial sweeteners
.

The relative contribution of different types of foods to total intake of artificial sweeteners

Next, the researchers analyzed
the association between sweetener intake and cardiovascular disease risk.
During the follow-up period, a total of 1502 cardiovascular events occurred, including 730 coronary heart disease events (including 143 myocardial infarction, 75 acute coronary syndromes, 477 angioplasty and 277 angina), and 777 cerebrovascular disease events (including 203 strokes and 598 transient ischemia).

Overall, a high total intake of artificial sweeteners was associated with a 9% increased risk of cardiovascular disease (RR, 1.
09; P = 0.
03).

The absolute incidence was 346 cases per 100,000 person-years in high-ingestion groups, compared with 314 cases
per 100,000 person-years in non-ingested groups.

Association between artificial sweetener intake and cardiovascular disease risk

The researchers also observed a closer association between artificial sweetener intake and the risk of cerebrovascular disease (hazard ratio, 1.
18; P = 0.
002).

Aspartame intake was associated with an increased risk of cerebrovascular disease (hazard ratio, 1.
17; P = 0.
02).

Acesulfame potassium and sucralose were associated with an increased risk of coronary heart disease (hazard ratio 1.
40; P = 0.
02 and 1.
31; P = 0.
05, respectively).

Different types of cardiovascular disease are also directly related
to sweetener intake.
Analysis found a direct association between sucralose intake and the risk of angioplasty (n=477; hazard ratio, 1.
60; P=0.
004), while total sweetener intake was directly associated with transient ischaemic events (n=598; hazard ratio, 1.
18; P=0.
006).

Similar to previous findings, their study also found a statistically significant association between sweeteners in beverages and cardiovascular disease risk (P=0.
02).

In addition, aspartame in beverages was statistically significantly associated with the risk of coronary heart disease (P=0.
03).

Another important finding was that substitution analysis showed that substitution of added sugars with artificial sweeteners did not reduce the risk of cardiovascular disease (hazard ratio, 1.
00; P = 0.
28).

Overall, these results suggest that higher intake of artificial sweeteners is associated
with an increased risk of cardiovascular disease.

Therefore, artificial sweeteners may be a modifier risk factor
for preventing cardiovascular disease.
At the same time, it also suggests that these food additives, which have been widely accepted and accustomed to by people, may not be healthy and safe alternatives
.
This provides an important basis
for the re-evaluation of artificial sweeteners by authoritative agencies.
This also reminds us ordinary consumers to be more cautious
when choosing sugar-free beverages.

References

[1] WHO.
Guideline: Sugars intake for adult and children.
Geneva:World Health Organization; 2015.
http://public.
eblib.
com/choice/ publicfullrecord.
aspx?p=2033879

[2] Debras C, Chazelas E, Sellem L, Porcher R, Druesne-Pecollo N, Esseddik Y et al.
Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort BMJ 2022; 378 :e071204 doi:10.
1136/bmj-2022-071204

[3] Market Data Forecast.
Global artificial sweetener market by type (aspartame, acesulfame-K, monosodium glutamate, saccharin, and sodium benzoate), by application (bakery items, dairy products, confectionery, beverages, and other), by distribution channel(supermarkets & hypermarkets, departmental stores, convenience stores, and others) and by regional analysis (North America, Europe, Asia Pacific, Latin America, and Middle East & Africa) - global industry analysis, size, share, growth, trends, and forecast (2022-2027).
2022.
style="white-space: normal;margin: 0px;padding: 0px;box-sizing: border-box;">[4] Chazelas E, Debras C, Srour B, et al.
Sugary Drinks, Artificially-Sweetened Beverages, and Cardiovascular Disease in the NutriNet-Santé Cohort.
J Am Coll Cardiol.
2020; 76(18):2175-2177.
doi:10.
1016/j.
jacc.
2020.
08.
075

Responsible editor| Ying Yuyan