Cardiovasc disease inc with sweet drinks, including artificially-sweetened ones

 A recent analysis from the French cohort study, the NutriNet-Sante Study, found more cardiovascular disease in people drinking more sweet drinks, including those with artificial sweeteners (see sweet drinks inc cvd jacc2020 in dropbox, or /doi.org/10.1016/j.jacc.2020.08.075)

Details:

--the French NutriNet-Sante cohort study began in 2009 with regular online questionnaires focusing on physical activity, SES, anthropometry, and 3 validated 24-hour dietary recalls every 6 months

--104,760 people: mean age 43, 79% women, mean number of dietary records 6, BMI 24, current smokers 17%, family hx of CVD 32%

--baseline diabetes 1%, hypercholesterolemia 8%, hypertension 8% [ie, overall a quite young, healthy group, with normal BMI]

--sugary drinks: defined as at least 5% sugar (soft drinks, syrups, 100% juice, fruit drinks)

--artificially-sweetened beverages (ASBs): containing non-nutritive sweeteners

--above data were linked to the national health insurance system and the national mortality registry

--participants were divided into nonconsumers, lower consumers and higher consumers

    --for sugary drinks: lower consumers had median intake of 47 ml/d, higher consumers 185 ml/d

    --for ABs: lower consumers had median intake of 40 ml/d and higher consumers 177 ml/d

--outcomes: first incidence of stroke, TIA, MI, acute coronary syndrome, and angioplasty

--cases in the first 3 years of follow-up were excluded to avoid reverse causality bias (ie, the person was sick and therefore decided to drink ASBs, for example)

--1379 first incident cases of CVD between 2009-2019

Results:

--daily consumption of drinks: 

    --men: 119 ml sugary drinks, 17 ml ASBs

    --women: 97 ml sugary drinks, 22 ml ASBs

--compared with nonconsumers

    --higher consumers of sugar drinks had 20% increased risk of cardiovascular events, adjusted HR 1.20 (1.04-1.40)

        --and there was a significant increase from nonconsumers to lower consumers to higher consumers, p=0.009 for the trend

    --higher consumers of ASBs had 32% increased risk of cardiovascular events, aHR 1.32 (1.00-1.73)

        --and there was a significant increase from nonconsumers to lower consumers to higher consumers, p=0.03 for the trend

Commentary:

--there have been many studies finding that artificial sweeteners are no better (and maybe worse) than sugary ones:

    --a large population-based study in 10 European countries with 450K people found that both sugar-based and artificially-sweetened beverages (ASBs) were associated with higher all-cause mortality, circulatory disorder deaths, and deaths from digestive diseases, with ASBs being worse in the first 2 cases: see http://gmodestmedblogs.blogspot.com/2019/10/soft-drinks-increase-mortality.html , which also references similar findings in the US Health Professionals and Nurses' Health Studies, and the Women's Health Initiative Observational Study.

    --a small study assessed 17 obese pts (BMI 42) who had not used non-nutritive sweeteners before and were insulin-sensitive, gave them a 5-h oral glucose tolerance test preceded by consuming sucralose or water (cross-over design), and found that pre-ingestion of sucralose led to a 14% increased peak glucose after the glucose load, a 20% increase in insulin area under the curve, a 22% increase in peak insulin, a 7% decrease in insulin clearance, and a 23% decrease in insulin sensitivity (see obesity sucralose inc insulin secretion diab care 2013 in dropbox, or DOI: 10.2337/dc12-2221) 

   --and, artificial sweeteners are associated with profound changes in the microbiome in mice, and a strong association of these microbiome changes with development of glucose intolerance. human studies have found that non-diabetic people ingesting non-caloric artificial sweeteners had increases in BMI, blood pressure, hemoglobin A1c, and fasting glucose levels, along with changes in their microbiomes. And another found that humans ingesting sucralose had microbiome changes leading to diabetes when their microbiomes were transplanted into germ-free mice. see http://gmodestmedblogs.blogspot.com/2017/01/artificial-sweeteners-microbiome1.html . for a recent review, see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363527/ . the studies find the major changes being with saccharine and sucralose

    -- and, in this light, there was an interesting study on metformin (see dm metformin microbiome GUT 2014 in dropbox, or doi.org/10.1136/gutjnl-2013-305370), the 7th most prescribed medicine and the first choice for diabetics. This study was in mice, and found that those on metformin improved their glycemic profile, but significantly changed the gut microbiome to increase the bacterium Akkermansia. In another experiment, just increasing Akkermansia without using metformin also enhanced the mouse's glucose tolerance and decreased adipose tissue inflammation (chronic inflammation is associated with diabetes), suggesting that a potentially very important mechanism of action for metformin may be through its beneficial effect on the microbiome. (see http://gmodestmedblogs.blogspot.com/2014/10/heart-failure-microbiome.html  ).

--And, sugar-sweetened beverages are consumed regularly by lots of people: in 2014 26% of US adults consumed soda or fruit drinks or both at least once a day, and more than 40% in the age group 18-34 (see https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a2.htm ), with these beverages accounting for 40% of added sugars consumed. by 2016 it seems that consumption was decreasing some (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770750/ )

--there are concerns that though these sweeteners have zero calories, there could be weight gain and increased blood sugars for a variety of reasons: people may eat/drink more sweetened foods  "i can eat more dessert because i am drinking diet sodas"  (additionally, the other components of diet drinks may have calories and other components that are not particularly healthy ); by being much sweeter than sugar, they may lead to diet changes (plain but healthy foods, such as vegetables or fruits, may be of less interest), and these potent sweeteners may encourage sugar craving and sugar dependence. Also,   the microbiome changes mentioned above may be important: there is the brain-gut connection whereby bacteria in the gut can produce neurotransmitters or modify neurotransmitter catabolism, change vagal signaling in the brain, or directly affect the hypothalamic/pituitary axis (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005194/#:~:text=The%20gut%20microbiota%20has%20been,activation%20of%20the%20HPA%20axis. ), and there may be both a neuronal response to eating highly sweetened foods through the mesolimbic dopamine system as well as gut triggering of hunger pathways

    --and studies have found that consumers of non-nutritive sweeteners may well gain significant weight: see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892765/#:~:text=Surprisingly%2C%20epidemiologic%20data%20suggest%20the,in%20the%201980s%20%5B18%5D.

--also, as a related issue, sugary drinks also often contain high-fructose corn syrup, which raises uric acid levels and potentially the risk of cardiovascular disease (see http://gmodestmedblogs.blogspot.com/2020/06/new-gout-management-guidelines.html  and http://gmodestmedblogs.blogspot.com/2019/04/uric-acid-lowering-cardiovasc-benefit.html

limitations:

--not much granular details about the participants in terms of their actual diets, exercise, or other socioeconomic variables.  they did control for age, sex, BMI, sugar intake from other dietary sources, smoking status, educational level, physical activity, family history of cardiovascular disease, and intakes of alcohol, fruit/veges, red and processed meat, nuts, whole grains, legumes, saturated fatty acids, sodium, as well as diabetes, dyslipidemia, hypertension, hypertriglyceridemia, and treatments for these conditions. But no data were provided about the actual diet composition, and the people in the study were young (mean age 43), nonobese (median BMI 24), and had few comorbidities (highest was hypertension and hyperlipidemia, neither defined specifically, and still only 8%). Even with advanced mathematical modeling, will these results really apply to a 67yo person from a different (and not well-represented in this study) ethnicity, with a culturally different diet, who has obesity, hypertension, hyperlipidemia, underlying heart disease.... and on many meds???

--the study was based on self-reported activities, including diet, so might not truly reflect actual consumption (though perhaps it is more likely that sugar/ASB consumption is understated)

    --but, at least this is a huge study, with frequent assessments of diet and other parameters, so is a much more accurate representation of what the participants were doing over tjme than some large data-mining studies

--no granular breakdown on the cardiovascular outcomes, and having a stroke is likely worse than having an angioplasty (both included in the combination CVD outcome)

so, i think the main message in this very large data-mining study is that both types of sweeteners (sugar and artificial ones) are not so good, and this is consistent with several prior studies. 

Though there have been several prior studies suggesting that ASBs are not healthy, and may well be deleterious even in diabetics, many diabetics and overweight/obese people (and perhaps many clinicians??) may think that diet drinks are better than sugary drinks. and, my experience has been that the low-hanging fruit (??) here for decreasing sugar and ASB intake is stopping soft drinks and fruit juices. water works well. though some people like to flavor the water with small amounts of a fruit juice (as in harm reduction: and the smaller amount of fruit juice, likely the better)...

geoff

 

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