Artificially Sweetened Soft Drinks May Increase the Risk of Stroke

This week JAMA published an epidemiological study of 451,743 Europeans from 10 countries which suggested there is an increased risk of myocardial infarction and ischemic stroke in persons who consume at least 1 glass of artificially sweetened soft drink per day (relative risk increase: 1.41). There was also an association with overall death rate (relative risk 1.26).

For a comparison, the risk of stroke in smokers is increased by a relative risk of about 2.34 in a prior German study (PROCAM). So, smoking increases the risk of stroke only about two and a half times more than artificially sweetened soft drinks usage may do.

The effect was robust and did not go away when factors such as BMI / obesity were taken into account, lessening the effect of any correlation of use of diet drinks in those who wish to lose weight.



Association Between Soft Drink Consumption and Mortality in 10 European Countries

Amy Mullee, PhD; Dora Romaguera, PhD; Jonathan Pearson-Stuttard, BMBCh; et al Vivian Viallon, PhD3; Magdalena Stepien, PhD3; Heinz Freisling, PhD3; Guy Fagherazzi, PhD; Francesca Romana Mancini, PhD; Marie-Christine Boutron-Ruault, MD; Tilman Kühn, PhD; Rudolf Kaaks, PhD; Heiner Boeing, PhD; Krasimira Aleksandrova, PhD; Anne Tjønneland, MD; Jytte Halkjær, PhD; Kim Overvad, MD; Elisabete Weiderpass, MD; Guri Skeie, PhD; Christine L. Parr, PhD; J. Ramón Quirós, MD; Antonio Agudo, PhD; Maria-Jose Sánchez, MD, PhD; Pilar Amiano, MS; Lluís Cirera, MD; Eva Ardanaz, MD; Kay-Tee Khaw, MB; Tammy Y. N. Tong, PhD; Julie A. Schmidt, PhD; Antonia Trichopoulou, MD; Georgia Martimianaki, MSc; Anna Karakatsani, MD; Domenico Palli, MD; Claudia Agnoli, MSc; Rosario Tumino, MD; Carlotta Sacerdote, MD; Salvatore Panico, MD; Bas Bueno-de-Mesquita, MD7,; W. M. Monique Verschuren, PhD; Jolanda M. A. Boer, PhD; Roel Vermeulen, PhD; Stina Ramne, MSc; Emily Sonestedt, PhD; Bethany van Guelpen, MD; Pernilla Lif Holgersson, PhD; Konstantinos K. Tsilidis, PhD; Alicia K. Heath, PhD; David Muller, PhD; Elio Riboli, MD; Marc J. Gunter, PhD; Neil Murphy, PhD

JAMA Intern Med. Published online September 3, 2019. doi:10.1001/jamainternmed.2019.2478

Importance Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date.

Objective To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality.

Design, Setting, and Participants This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018.

Exposure Consumption of total, sugar-sweetened, and artificially sweetened soft drinks.

Main Outcomes and Measures Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors.

Results In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio [HR], 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001).

Conclusions and Relevance This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.


Heliconias are striking plants when in bloom. What we see most as the flowers are specially shaped and pigmented leaves, called bracts. The much smaller flowers are nestled within the brachts and may last less than 24 hours each, but they too can be striking. See the indigo flower in the pictures.

Friday bioRxiv prepost review: "Is Vagus Nerve Stimulation Brain Washing?"

In the bioRxiv preprint here, the authors find that the type of vagus nerve stimulation used to treat intractable epilepic seizures may open the blood-brain barrier to penetration by the cerebrospinal fluid, increasing the "washing" of fluid through the cells of the brain. The cause of this effect remains unclear. The effect on CSF penetration is not likely to cause any of VNS's known effects on epilepsy. Instead, because the vagus nerve is already known to be intimately involved with such autonomic functions as the body's circulation, VNS's effects of brain fluid flows is more likely to be a consequence of vagus nerve action on the circulation of the CSF lymphatic system (the "adrenergic signaling" mentioned in the article).

Where would this effect be useful clinically? This is not clear, but the possibility of increasing the effects of intrathecal chemotherapy on certain cancers comes to mind.



Is Vagus Nerve Stimulation Brain Washing?

Kevin P. Cheng1*, Sarah K. Brodnick1*, Stephan L. Blanz1, Weifeng Zeng2, Jack Kegel1, Jane A.
Pisaniello1, Jared P. Ness1, Erika Ross3, Evan N. Nicolai1,4, Megan L. Settell1,4, James K.
Trevathan1,4, Samuel O. Poore1,2, Aaron J. Suminski1,5, Justin C. Williams1,5*, Kip A. Ludwig1,5*

One Sentence Summary: Cervical vagus nerve stimulation using clinically derived parameters enhances
movement of cerebrospinal fluid into the brain parenchyma presenting a previously unreported effect of vagus
nerve stimulation with potential clinical utility.

Abstract: Vagal nerve stimulation (VNS) is an FDA approved treatment method for intractable epilepsy,
treatment resistant depression, cluster headaches and migraine with over 100,000 patients having received
vagal nerve implants to date. Moreover, evidence in the literature has led to a growing list of possible clinical
indications, with several small clinical trials applying VNS to treat conditions ranging from neurodegenerative
diseases to arthritis, anxiety disorders, and obesity. Despite the growing list of therapeutic applications, the
fundamental mechanisms by which VNS achieves its beneficial effects are poorly understood and an area of
active research. In parallel, the glymphatic and meningeal lymphatic systems have recently been proposed and
experimentally validated to explain how the brain maintains a healthy homeostasis without a traditionally defined
lymphatic system. In particular, the glymphatic system relates to the interchange of cerebrospinal fluid (CSF)
and interstitial fluid (ISF) whose net effect is to wash through the brain parenchyma removing metabolic waste
products and misfolded proteins from the interstitium. Of note, clearance is sensitive to adrenergic signaling, and
a primary driver of CSF influx into the parenchyma appears to be cerebral arterial pulsations and respiration. As
VNS has well-documented effects on cardiovascular and respiratory physiology as well as brain adrenergic
signaling, we hypothesized that VNS delivered at clinically derived parameters would increase CSF influx in the
brain. To test this hypothesis, we injected a low molecular weight (3 kD) lysine-fixable fluorescent tracer (TxRed)
into the CSF system of mice with a cervical vagus nerve cuff implant and measured the amount of CSF
penetrance following VNS. We found that the clinical VNS group showed a significant increase in CSF dye
penetrance as compared to the naïve control and sham groups. This study demonstrates that VNS therapeutic
strategies already being applied in the clinic today may induce intended effects and/or unwanted side effects by
altering CSF/ISF exchange in the brain. This may have broad ranging implications in the treatment of various
CNS pathologies.

Immunization Policies by Country

Vaccination policy by country:
  orange -- Mandatory vaccination
  blue -- Voluntary vaccination
  green -- Vaccination not mandatory, but proof of vaccination needed to enroll in public schools

There's been some discussion this year in the news, because of the increase in measles cases this year, about public health regulations and their relation to vaccination rates. Many countries do not require vaccination, but still have good vaccination rates. There is some tension between parental autonomy and the public health of the population, one that is solved for the most part when parents are sufficiently rational about their children's health.

Map from Wikipedia, here.

Would Eddie the bigwave surfer go .. google?

Apparently, Google thinks so! They memorialized Eddi Aikau gave him a doodle on the Google search home page today. Here.

Artificially Sweetened Soft Drinks May Increase the Risk of Stroke

This week JAMA published an epidemiological study of 451,743 Europeans from 10 countries which suggested there is an increased risk of m...