BY MARIA BURKE | 18 OCTOBER 2023
New study suggests artificial sweeteners may be linked to depression, but more research is needed.
Health concerns around artificial sweeteners abound, but evidence remains patchy. Now, a study has suggested an increased risk of depression, following reports indicating associations with cardiovascular events and lowered immunity.
In a long-term study investigating ultra-processed foods (UPFs) and depression, a team from Harvard Medical School, US, found that of all the food categories included, only artificial sweeteners were associated with an increased risk.
The team assessed the diet of 31,000 women every four years and discovered more than 4,000 were diagnosed with depression or prescribed antidepressants.
Women who consumed nine ‘portions’ or more of sweeteners daily were about 50% more likely to be depressed, compared with those consuming four portions or less.
However, the study has several limitations. The participants with higher intakes of UPFs also had higher BMIs, were more likely to smoke and have chronic diseases, and less likely to exercise.
‘Food-frequency questionnaires, which were used in this study to measure UPF intake, can also only provide very limited information,’ says Gunter Kuhnle of the University of Reading, UK.
‘The study can only identify associations and not a causation. It is very possible that people with depression change their diet. It is also important to note that there are a wide range of different artificial sweeteners that are metabolised very differently and that there might be reverse causality.’
Cardiovascular risks?
A study earlier in 2023 raised concerns about artificial sweeteners and cardiovascular disease. A study by the Cleveland Clinic, US, of over 4,000 high-risk patients found those with higher levels of the sweetener erythritol were at greater risk of experiencing heart attacks and strokes. They also examined the effects of adding erythritol to blood or isolated platelets, revealing erythritol made platelets easier to activate and form a clot.
However, the Cleveland study used sweetener concentration ten times higher than the permitted amount in drinks in the UK and Europe. It also did not measure platelet function in blood from patients after consuming erythritol; it extrapolated from in vitro measurements to predict effects, says Tom Sanders, of King’s College London, UK.
‘It is also worth noting that there is only limited evidence that measurement of platelet aggregation on individuals can predict risk of CVD. The mechanism by which erythritol might affect platelet function is also unclear, especially as it is a relatively unreactive molecule’, he explains.
In a study on mice, a team at the Francis Crick Institute in the UK reported that consuming high quantities of the sweetener sucralose made the mice less able to activate T-cells – a type of immune cell – in response to cancer or infection with bacteria.
‘[This does not mean] that sucralose is harmful if consumed in the course of a normal balanced diet, as the doses we used in mice would be very hard to achieve without medical intervention,’ says Fabio Zani, co-first author. ‘The impact on the immune system we observed seems reversible and we believe it may be worth studying if sucralose could be used to ameliorate conditions such as autoimmunity, especially in combinational therapies.’
‘This paper is hugely important in showing that sucralose is not a molecule which simply has no action in the human body,’ says Daniel Davis, of Imperial College London, UK. ‘At high doses, it can lower the ability of T-cells to play their part in immune responses. There is evidence that it can do this by subtly changing the normal organisation of molecules in the surface of T-cells.’
Limitations remain
África González Fernández, of the Centro de Investigaciones Biomédicas (CINBIO), Spain, warns the study has several limitations such as the high doses used; the prolonged administration; and the findings being mostly from in vitro cultures.
‘There are hundreds of studies carried out with this substance and, except for changes in the microbiota, it has not been shown to cause any problems for human health. It is safe, non-carcinogenic and does not affect the immune system,’ she says.
One message seems clear: more research is needed. ‘Long-term observational studies and appropriately designed clinical trials are still needed to establish the evidence and to determine safe levels in an environment of increasing use of artificial sweeteners,’ concludes Nita Forouhi of the MRC Epidemiology Unit at the University of Cambridge, UK.
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