Artificial sweeteners and stroke

Artificial sweeteners and stroke

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You forwarded this message on Wed 2/27/2019 7:19 AM

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Geoff A. Modest, M.D.

Wed 2/27/2019 7:17 AM

Geoff A. Modest, M.D.

Analysis of the Women’s Health Initiative Observational Study found that artificially sweetened beverages are associated with increased risk of stroke, coronary heart disease, and all-cause mortality (see stroke and artif sweeteners stroke2019 in dropbox, or DOI: 10.1161/STROKEAHA.118.023100)

Details

-- 81,714 women in the WHI Observational Study, a multicenter longitudinal study of the health of 93,676 postmenopausal women aged 50 to 79 at baseline, enrolled in the 1990s (this was a long-term observational wing of WHI, as opposed to the clinical trials with hormone therapy, dietary modification, calcium/vitamin D)

-- 64% were infrequent consumers (never or <1/week) of artificially sweetened beverages (ASBs), 5.1% consumed at least 2 ASBs/d.

--85% white/7% black/4% Hispanic

-- comparing those drinking >1 ASB/d vs rarely drinking ASB: more smoking (8% vs 5%), less alcohol (60% vs 70% drinking), higher BMI (BMI >30 in 45% vs 21%), more HTN/diabetes/history cardiovasc dz, less exercise, less healthy eating index, and more calorie intake (1617 vs 1453 kcal/d), but younger (61 vs 64 yo)

-- 79% of those consuming >1 ASB per day never or rarely consumed regular soda, 9% consumed at least one regular soda a day  

--overall there were 2838 fatal and nonfatal strokes, 2227 ischemic strokes, 422 hemorrhagic strokes, 3618 CHD events, and 15,005 deaths during 11.9 years of followup

Results:

-- comparing those at the highest level of ASB consumption to those who never or rarely drank, in multivariate analysis (controlling for age, race/ethnicity, education, diabetes, history of cardiovascular disease/hypertension/taking cholesterol-lowering medications, BMI as a continuous variable, smoking, alcohol, physical activity, and diet quality):

    -- all stroke: 23% increase, HR 1.23 (1.02-1.47)

    -- ischemic stroke: 31% increase, HR 1.31 (1.06-1.63)

    -- coronary heart disease: 29% increase, HR 1.29 (1.11-1.51)

    -- all-cause mortality: 16% increase, HR 1.16 (1.07-1.26)

-- in women with no prior history of cardiovascular disease or diabetes, high consumption of ASB was associated with:

    -- more than twofold increased risk of small artery occlusion ischemic stroke, HR 2.44 (1.47-04), and an overall increase in the fully adjusted model of 81%, HR 1.81 (1.18-2.80)

    -- no difference if the patient had or did not have hypertension

-- in women with BMI >30: twice the risk of ischemic stroke, HR 2.03 (1.38-2.98), with a less clear risk in those with BMI <30, but an increased risk of all-cause mortality only in those with BMI <30.

Commentary:

--overall there was a significantly greater likelihood of all endpoints (except hemorrhagic strokes) in those with the highest intake of ASBs, controlling for demographics, risk factors, comorbidities, and behavioral variables.

--the above subclassification of strokes found a particular association between ASBs and small artery occlusion ischemic strokes, and this was independent of a diagnosis of hypertension or diabetes. I would add the strong caveat that the risk of stroke is also likely related to a gradient of higher blood pressure or sugar along a continuum and not a discrete cutpoint. For example, the cutpoint of A1c=6.5 is a nice clean number, but cardiac events seem to start increasing much sooner (esp in men, where 5.5-6.0 is related to increased CVD risk, more like 6.0-6.5 in women). So, especially in those women who are obese and more predisoposed to hyperglyemia and hypertension, they may well have increased blood sugars and A1c’s at a subdiagostic level for diabetes, yet may have increased CVD events related to this. And they would not be picked up by the formal diabetes diagnosis. And similar argument for hypertension

-- there are pretty profound effects of non-caloric artificial sweeteners on the microbiome:

    --see http://gmodestmedblogs.blogspot.com/2017/01/artificial-sweeteners-microbiome1.html  which reviews evidence showing that there are profound changes in the microbiome, which predispose people (and mice) to diabetes as well as weight gain

    --see http://gmodestmedblogs.blogspot.com/2018/04/non-nutritive-food-additives-and-c.html about the artificial sugar trehalose, associated with more virulent C difficile infections

--there were some racial difference: eg black women had more strokes, white women had more CHD.  In a large observational study, it is hard to determine why this is.  is it because of limitations of their data (eg as above, where the categories of “diabetes” etc do not reflect the actual blood sugar continuum). Is it because of important variables not assessed in their database? Is it because the questionnaires are not answered accurately? Or that the eating habits (including ASBs), for example, are different on the day the patient was asked and 2 months later? Etc etc

--limitations: this is an observational study and unable to attribute causation. eg, were women taking ASBs fundamentally different from those not doing so? Were they trying to lose weight, and consuming ASBs actually made them think it was okay to overeat unhealthy foods (eating lots of fast foods, but thinking it was okay since they had a diet soda with it??)...

So, this adds to the increasing literature that consuming artificial sugars is bad. Undoubtedly has bad effects on the gut microbiome. And this can have very bad effects on patients’ health. It is somewhat reassuring that in this long-term study, 2/3 of women had no or rare ASB consumption. For better or worse, the best liquid to drink is water (if not contaminated…). And, of course, coffee is healthy (see http://gmodestmedblogs.blogspot.com/2019/01/coffee-and-decreased-mortality.html )

geoff​

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