More Evidence Ties Diet Drinks to Greater Stroke Risk

Damian McNamara

February 21, 2019

Drinking artificially sweetened beverages is linked to increased risk for ischemic stroke, coronary heart disease, and all-cause mortality in women, new research shows.

Among almost 82,000 participants in the Women's Health Initiative Observational Study, risk for fatal and nonfatal stroke was 23% higher among women who self-reported drinking the most diet beverages — two or more per day — compared to the women who consumed the least. The latter group drank none or less than one of these beverages per week.

The results reinforce similar associations from other recent studies and add a novel finding — the group with the highest consumption had an 81% elevated risk for small artery occlusion (SAO).

"That's the most exciting finding — that's where the high risk was, in these small artery occlusions," principal investigator Yasmin Mossavar-Rahmani, PhD, RD, associate professor, Division of Health Promotion and Nutrition Research, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York City, told Medscape Medical News.

The findings were published online February 14 in Stroke.

Inconsistent Data

As previously reported by Medscape Medical News, a 2017 study of nearly 4400 participants in the Framingham Heart Study Offspring Cohort showed an association between high intake of artificially sweetened beverages and risks for dementia and cardiovascular events, including stroke.

"That really sparked my interest in doing this study," Mossavar-Rahmani said. "So we decided to look at the link between artificially sweetened beverage consumption and stroke risk, cardiovascular disease, and all-cause mortality."

A previous study of participants in the Women's Health Initiative found a 30% increase in composite cardiovascular events and all-cause mortality associated with drinking two or more servings of artificially sweetened beverages per day.

However, data regarding artificially sweetened beverage consumption and cardiovascular disease events from other studies are inconsistent, the current researchers note.

Mossavar-Rahmani and colleagues examined data for 81,714 participants who entered the Women's Health Initiative Observational Study from 1993 to 1998 when they were aged 50 to 79 years.

Three years after their baseline clinical visit, participants underwent a physical examination in which blood was drawn.

They also completed questionnaires that asked about their consumption of artificially sweetened beverages during the prior 3 months. Examples included Diet Coke and diet fruit drinks in 12–fluid ounce cans.

Frequent vs Infrequent Consumers

The investigators classified consumption levels into nine categories, with frequency ranging from never to six times a day. They also evaluated any effect of race/ethnicity or body mass index (BMI) on the associations in the study.

The researchers also assessed sugar-sweetened beverage consumption and consumption of other nutrients on the basis of responses to the Women's Health Initiative Food Frequency Questionnaire.

Most participants (79%) who consumed two or more artificially sweetened beverages per day never or rarely drank regular soda, indicating there were few women who regularly consumed both types of beverages.

Cox regression analyses controlled for multiple covariates, including age, race/ethnicity, education, history of diabetes mellitus, history of cardiovascular disease, hypertension, smoking, alcohol, physical activity, and a diet quality variable.

The majority of participants (64%) were infrequent consumers, defined as never drinking an artificially sweetened beverage or drinking less than one per week. In contrast, only 5% consumed two or more such diet beverages per day.

Participants who consumed a high level of artificially sweetened beverages were younger and more educated, and they reported higher income compared with the group with the lowest consumption. In addition, they engaged in lower levels of exercise, were more likely to be overweight or obese, had a lower quality of diet, and were more likely to have a history of stroke.

The mean follow-up for the study was almost 12 years.

Fewer Calories, More Risk?

Compared with the lowest level of consumption, drinking two or more artificially sweetened beverages per day was associated with a greater overall risk for fatal and nonfatal stroke (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02 – 1.47).

Risk for ischemic stroke was 31% higher for those participants (HR, 1.31; 95% CI, 1.06 – 1.63). In addition, these women had a 29% greater risk for coronary heart disease (HR, 1.29; 95% CI, 1.11 – 1.51) and 16% greater risk for all-cause mortality (HR, 1.16; 95% CI, 1.07 – 1.26).

Across the entire cohort, 2838 fatal and nonfatal strokes, 2227 ischemic strokes, 422 hemorrhagic strokes, 3618 coronary heart disease events, and 15,005 deaths occurred during follow-up after year 3.

The incidence of hemorrhagic stroke did not vary significantly across the levels of diet beverage consumption.

"The finding that in women with BMI ≥30, high consumption of diet drinks was associated with an increased risk of all end points except hemorrhagic stroke in women is notable," the researchers write.

Consumption of two or more artificially sweetened beverages daily was linked to greater odds for an SAO compared to the lowest consumption (HR, 1.81; 95% CI, 1.18 – 2.80) in analyses adjusted for other covariates.

The risk for SAO was even greater for high consumers in sensitivity analyses that excluded participants with diabetes mellitus or cardiovascular disease (HR, 2.44; 95% CI, 1.47 – 4.04).

Hypertension did not seem to modify risk for SAO. Among the high consumers with hypertension, the HR was 2.38 (95% CI, 1.25 – 4.55; P = .009). For those without hypertension, the HR was similar, at 2.45 (95% CI, 1.09 – 5.50; P = .030).

"Therefore, the increased risks of stroke and especially SAO are not likely to be mediated by diabetes mellitus or hypertension," the investigators write.

Drinks and Demographics

Interestingly, there was no significant interaction with age in the study. However, the researchers report some associations that varied with BMI and race/ethnicity.

High consumption of artificially sweetened beverages was significantly linked to increased ischemic stroke risk only among women with a BMI of 30 kg/m2 or more (HR, 2.03; 95% CI, 1.38 – 2.98).

High consumption was also associated with increased all-cause mortality, but only in participants with a BMI of less than 30 kg/m2.

When it comes to increased risk, "there is something there for everyone, unfortunately," Mossavar-Rahmani said.

The investigators also found that black women who consumed more artificially sweetened beverages had higher risk for ischemic stroke compared with women from other race/ethnic groups (HR, 3.93; 95% CI, 1.87 – 8.26).

There was also a significant interaction between black race and all stroke (ie, fatal and nonfatal stroke) (P = .0006) and ischemic stroke (P = .002).

"So the question is why African Americans had the higher risk," Mossavar-Rahmani said.

Ischemic stroke tends to occur earlier in African Americans, and African Americans are at twice the risk of dying from stroke compared to whites, she added.

"They also tend to have more diabetes, high blood pressure, and smoking — things we controlled for — but there could be unknown genetic factors that play into this as well," she said.

Worth Discussing

Although clinicians are often pressed for time to address all health and wellness messages during a clinical visit, Mossavar-Rahmani suggested that diet drink consumption could be worth discussing with patients.

"It makes sense to have a conversation with patients and see what else they can do toward healthier drinking habits," she said. "Clinicians should read these findings and the previous findings and make up their minds" about sharing the results with patients.

"It seems sensible to have the discussion in any case and not to assume that high levels are harmless," she added.

Future research is warranted to evaluate why all stroke (ie, fatal and nonfatal stroke) and ischemic stroke among high consumers of diet beverages were significantly associated with being black as opposed to other races.

Another unanswered question is why white postmenopausal women who consumed higher amounts of such beverages had a greater risk for coronary heart disease compared with black women.

The study was observational, a potential limitation that could introduce residual confounding. In addition, the diet quality variable (Healthy Eating Index–2005) and self-reported physical activity levels may not have precisely measured the quality of diet or physical activity.

Strengths of the research include information on stroke and stroke subtypes, the large population size, and the commitment of the women who enrolled in the study.

Mossavar-Rahmani has recently begun a randomized clinical trial evaluating diet and cognitive decline. The aim is to test whether consuming a healthy multicultural diet high in fruits and vegetables can reduce risk for cognitive decline and, eventually, risk for Alzheimer's disease in a multicultural population of 40- to 65-year-olds.

"Jury's Still Out"

Asked by Medscape Medical News to comment on the findings, Vincent Thijs, MD, PhD, head of stroke at Austin Health and co-head of the Stroke Theme at the Florey Institute of Neuroscience and Mental Health in Heidelberg, Victoria, Australia, said this large observational study was "interesting" and well-executed.

"It adds to a growing literature of studies reporting on an association of drinking with increased risk of stroke, heart attacks, and deaths," he said. However, "Are these findings true and convincing? I think the jury is still out."

More research into mechanisms behind these associations and a more precise dose-response effect are warranted, he added.

"We are still uncertain whether the effect is directly related to consuming diet drinks," Thijs said.

One possiblity is that women who start to consume diet sodas or diet fruit drinks often do so because of health problems, perhaps on the advice of their physicians or relatives or because of their own perceptions regarding health or disease, he said.

Thijs added that the current study cannot entirely rule out this alternative explanation.

Important Contribution?

"Evidence regarding the negative health effects of low calorie nonnutritive sweeteners is relatively inconclusive but growing," Hannah Gardener, ScD, Department of Neurology, the Miller School of Medicine, University of Miami, in Florida, and Mitchell S. V. Elkind, MD, Department of Neurology, the Vagelos College of Physicians and Surgeons, Columbia University, New York City, write in an accompanying editorial.

The current study "is an important contribution to this epidemiological literature on the relationship between artificially sweetened beverages and stroke, coronary heart disease and mortality," they write.

Frequent consumption of artificially sweetened beverages during midlife and late life has now been associated with an increased risk for vascular events in multiple observational studies, Gardener and Elkind note. "But what remains unclear is the causal nature of these associations," they say.

"Perhaps most interesting were the analyses stratified by body mass index category," they write.

"Heavy artificially sweetened beverage consumption was associated with an increased incidence of stroke only among the obese, with no association evident among those of normal body mass index or overweight.

"In contrast, all-cause mortality was increased among frequent artificially sweetened beverage consumers who were normal weight or overweight but not definitely among those who were obese," the editorialists write.

"We should emphasize water as the healthiest substitute for sugar sweetened beverages" until more evidence clarifies who, if anyone, benefits from consumption of artificially sweetened beverages, they note.

If these diet drinks are used to wean people off sugar-sweetened drinks, "it should be viewed as a time-limited intermediate in the transition to water and other healthier beverages," Gardener and Elkin write.

The Women's Health Initiative was funded by the National Heart, Lung, and Blood Institute, by the National Institutes of Health, and by the US Department of Health and Human Services. The editorial was supported by the National Institute of Neurological Disorders and Stroke. Mossavar-Rahmani, Thijs, and the editorialists report no relevant financial relationships.

Stroke. Published online February 14, 2019. Abstract, Editorial

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