Sugar-Sweetened Beverages, Diet Coke & Health. Part I.

14 03 2010

At Medical and Technology of Joseph Kim, the upcoming Grand Rounds host, I saw the blog post “Need your help on Facebook to get Diet Coke to Donate $50,000 to the Foundation for NIH”.

National Heart Lung and Blood Institute has started a national campaign in the US, The Heart Truth®. They issued a challenge in support of heart health, raising awareness on the fact that  heart disease is the #1 killer of women, to identify risk factors and take action to lower them. Diet Coke is one of their corporate-partners, helping to spread the word through visibility on 6.7 billion packages of Diet Coke featuring The Heart Truth and Red Dress symbol. It has also started a Facebook cause: Diet Coke will donate $0.50 for every person that joins the cause and $1.00 for every person that donates $1, for a total donation of up to $50,000!

O.k. Donation Fine, NIH fine, but Coca Cola as a main sponsor to raise awareness against heart disease?? Its almost feels like a tobacco company raising awareness against lung cancer. It is as odd as McDonalds, Lego & Mars preaching online advertising awareness to kids...

You could object that any money to raise awareness is  a welcome bonus and that diet coke, unlike normal coke, doesn’t contain any calories. But then you could ask whether diet coke is really healthy… Plus Coca Cola does sell a lot of beverages with loads of sugar, with a possible adverse effect on health, including cardiovascular disease (see below). It looks a lot like hypocrisy to me, meant only to improve the BRAND.

Well, I was to write about sweetened beverages anyway, since I came across several interesting news items the last weeks.

Sugar-Sweetened Beverages Have Major Effects on Diabetes and Cardiovascular Health

During the joint EPI/NPAM Conference (Cardiovascular Disease Epidemiology and Prevention &- Nutrition, Physical Activity and Metabolism), Mar 2-5, 2010 (link), Litsa Lambrakos presented a posterSugar-Sweetened Beverage Consumption and the Attributable Burden to Diabetes and Coronary Heart Disease” that was covered in a press release and in the media (Elsevier Global Medical News; All Headline News)

Based on data from several large observational studies demonstrating a link between higher rates of sugar-sweetened beverages (SSB) consumption and subsequent risk of incident diabetes, Lambrakos and colleagues assumed that daily consumption of SSBs is associated with an increased risk of incident diabetes (RR 1.32 for those with daily consumption compared with adults consuming less than one sugar-sweetened beverage per month).  Next they estimated that the increased consumption of sugar-sweetened beverages (including sugar-sweetened soda, sport and fruit drinks) between 1990 and 2000 contributed to 130,000 new cases of diabetes, 14,000 new cases of coronary heart disease (CHD), and 50,000 additional life-years burdened by coronary heart disease over the past decade. They derived these data from the 1990-2000 National Health and Nutrition Examination Survey (NHANES) on consumption of sugar-sweetened beverages, combined  with the CHD Policy Model, a computer simulation of heart disease in U. S. adults aged 35-84 years.

Through the model, the researchers also estimated that the additional disease caused by the drinks has increased coronary heart disease healthcare costs by 300-550 million U.S. dollars between 2000-2010. This is probably an underestimation, because it does not account for the increased costs associated with the treatment and care of patients with diabetes alone.

How does this ($300.000.000-$550.000.000) compare to the $50,000 (max) that Coca Cola is willing to contribute to The Heart Truth?

Admitted, the comparison is not entirely fair. There are far more soft drinks than the sodas from Coca Cola. More importantly, the reliability of the  figures is highly dependent on the accuracy of the assumptions. Furthermore it is hard to review a study that is not yet published.

Other studies on possible harm of SSB consumption. 1. Effects on BMI, overweight & obesity.

To get an idea about the evidence on the ‘harm’ of SSB I did a quick search in PubMed (see PubMed tips).

First I searched for secondary (aggregated) sources.

((Dietary Sucrose AND beverages) OR soft drink* OR sugar-sweetened beverag* OR soda*[tiab]) AND “systematic”[Filter]

This yielded 27 hits.

Five Publications centered on the effect of beverages on weight, obesity or BMI.

The effect on overweight seems the most obvious side-effect of SSB’s. First the increase in obesity over time has been paralleled by an increase in soft drink consumption. Second the daily sweetener consumption in the United States increased by 83 kcal per person, of which 54 kcal/d  from soda. If these calories are added to the normal diet without reducing intake from other sources, 1 soda/d could lead to a weight gain of 6.75 kg in 1 year. [refs in 2]

Still the evidence is not that clear.

Malik [2], and an almost overlapping systematic review [3] conclude that large cross-sectional studies, well-powered prospective cohort studies with long follow-up, and short-term experimental studies (including 2 RCT’s), show a positive association between greater intakes of SSBs and weight gain and obesity in both children and adults and yield sufficient evidence for public health strategies to discourage consumption of sugary drinks as part of a healthy lifestyle.

Two later reviews [4,5] point out that Malik et al. had erroneously concluded that the evidence was ‘strong’, because “several studies were reported as positive when only a selected sub-group had a positive result, or classified as ‘positive non-significant’ where coefficients are near zero and P values in excess of 0·2. Furthermore, the results of two studies were confounded by the inclusion of diet soft drinks.”[4]

On the contrary, Forshee et al [4] conclude that the  association between SSB consumption and BMI was near zero. Interestingly, the funnel plot analysis was consistent with publication bias against studies that do not report statistically significant findings!

Gibson [5] concludes that that the effect of SSB on body weight is small except in susceptible individuals or at high levels of intake. She also points out that the totality of evidence is dominated by American studies (including the positive NHANES study), “that may be less applicable to the European context where consumption is substantially lower and composition or formulation may differ (high-fructose corn syrup v. sucrose, proportion of diet v. non-diet, etc).”
Indeed in a systematic review primarily including European studies [6], overweight was not associated with the intake of soft drinks, but with lower physical activity and more tv watching time.

Thus the effect of SSB (alone) on BMI and overweight is inconclusive, based on the current body of evidence.

It is not excluded though that high intake of SSB alone or regular consumption of SSB in combination with other unhealthy lifestyle factors (unsaturated fat, lower physical activity) do contribute to obesity.

Since lack of sleep is also unhealthy (and possibly obesogen), I will leave it here.

Next time I will discuss any cardiovascular or other harmful effects of sugar sweetened beverages ànd diet sodas.

Meanwhile enjoy the sugar and coca cola video below.

Whatever the evidence, daily consumption of SSB, with many calories and no nutritional value, doesn’t seem overtly healthy to me. I won’t allow my kids to drink soda as a habit.


  1. Litsa K Lambrakos, Pamela Coxson, Lee Goldman, Kirsten Bibbins-Domingo (2010). Sugar-Sweetened Beverage Consumption and the Attributable Burden to Diabetes and Coronary Heart Disease, poster  365, Joint Cardiovascular Disease Epidemiology and Prevention &- Nutrition, Physical Activity and Metabolism – Conference Mar 2-5, 2010.
  2. Malik VS, Schulze MB, & Hu FB (2006). Intake of sugar-sweetened beverages and weight gain: a systematic review. The American journal of clinical nutrition, 84 (2), 274-88 PMID: 16895873
  3. Wolff E, & Dansinger ML (2008). Soft drinks and weight gain: how strong is the link? Medscape journal of medicine, 10 (8) PMID: 18924641
  4. Forshee RA, Anderson PA, & Storey ML (2008). Sugar-sweetened beverages and body mass index in children and adolescents: a meta-analysis. The American journal of clinical nutrition, 87 (6), 1662-71 PMID: 18541554
  5. Gibson S (2008). Sugar-sweetened soft drinks and obesity: a systematic review of the evidence from observational studies and interventions. Nutrition research reviews, 21 (2), 134-47 PMID: 19087367
  6. Janssen I, Katzmarzyk PT, Boyce WF, Vereecken C, Mulvihill C, Roberts C, Currie C, Pickett W, & Health Behaviour in School-Aged Children Obesity Working Group (2005). Comparison of overweight and obesity prevalence in school-aged youth from 34 countries and their relationships with physical activity and dietary patterns. Obesity reviews : an official journal of the International Association for the Study of Obesity, 6 (2), 123-32 PMID: 15836463

Photo Credits

  1. Diet Coke:
  2. Sugar in Coca Cola:
They used data from the 1990-2000 National Health and Nutrition Examination Survey (NHANES) on consumption of sugar-sweetened beverages. She combined that with the Coronary Heart Disease Policy Model, a computer simulation of heart disease in U. S. adults aged 35-84 years.

CMV-infection, plaques and high blood pressure

26 05 2009

A recent experimental study shows that a common virus that hides (becomes latent) after infection can trigger high blood pressure, a leading cause of cardiovascular disease.

The virus is cytomegalovirus (CMV). It belongs to the herpesviruses, hence its alternative name Human Herpesvirus 5 (HHV-5). The herpesviruses have in common that they can become latent (dormant) for a long while. Herpes simplex virus-1 (HSV-1) and varizella zoster virus usually hide in nerves (neurons) and can cause cold sores and shingles respectively after reactivation.

Cytomegalovirus (CMV) can be transmitted by sputum and other bodily fluids. After infection, it stays within the host, hiding primarily in certain white blood cells serving as a reservoir for reactivation.

The study by Cheng et al, consisted of an experimental mouse study and in vitro experiments, using mouse CMV (MCMV) and human CMV (HCMV)

  1. In the in vivo experiment, 4 groups of mice -of 12 animals each- were treated as follows:
    • V: Mice in group 1 were infected by MCMV and fed a regular diet.
    • M: Mice in group 2 were mock-infected and fed a regular diet (control group).
    • V-HD: Mice in group 3 were infected by MCMV and fed a high cholesterol diet.
    • HD: mock-infected and fed a high cholesterol diet (control group).
      systolic diastolic
  2. After 6 weeks the blood pressure, measured in the carotid artery, was significantly enhanced in mice that were infected by the MCMV compared to mock-infected controls. Thus the blood pressure was significantly higher in V versus M and in V-HD versus HD mice. This was both true for the systolic and the diastolic blood pressure (see Fig).
  3. Atherosclerotic plaque formation in mouse aortas was only observed in V-HD mice (MCMV infection and high cholesterol diet together). 3 out of 12 mice showed plaques against 0 out of 12 mice in the other groups.
  4. The serum levels of all 3 pro-inflammatory cytokines tested, IL-6, TNF-α and MCP-1, were higher in the mice infected with MCMV (V-HD and V) than in the mock-infected groups fed with either diet.
  5. CMV infection induced renin and Ang II expression (in vitro cq in vivo). Renin is a rate limiting protein of Renin-Ang-II system and Ang II is the peptide that causes the blood vessels to constrict, thereby enhancing blood pressure.
  6. The renin production was only enhanced in kidney-cells containing CMV-particles.
  7. In mice infected with CMV, Ang II was also increased in serum and in artery tissues.
  8. MCMV RNA and DNA were present in blood vessels post infection. Mice produced the latency-related CMV transcriptional product I-E1.
  9. Next, in vitro experiments were carried out with human cells. Infection of human blood vessel endothelial cells with HCMV induced renin expression in a-dose dependent manner, without lysis of the cells (non-lytic infection). This means that viral gene expression takes place in the absence of a viral cytopathic effect. Only replicating forms of HCMV could induce renin.

Conclusion of the Authors:

“In summary, CMV infection alone caused a significant increase of arterial blood pressure. Enhanced expression of pro-inflammatory cytokines, renin and Ang II underlies the pathogenic mechanism of an active CMV infection to increase blood pressure and aggravate atherosclerosis. Thus, control of CMV infection to restrict development of hypertension and atherosclerosis may provide a new strategy to prevent cardiovascular diseases associated with HCMV infection.”

The present article provides interesting new insights into various mechanisms whereby CMV could ultimately cause cardiovascular disease. Many different assays were performed, both with mouse CMV in vivo and in vitro and with human CMV in vitro.

It should be noted however, that several of the reported findings are not new. CVM DNA and RNA have long been identified in atherosclerotic plaques. CMV and other herpesviruses were known to induce IL-6 and other pro-inflammatory interleukines. And a relation between CMV-infection and cardiovascular disease has been established in the past.

The main new findings are (1) that CVM-infection can raise blood pressure and (2) the demonstration of possible mechanisms involved in the increase of blood pressure: induction of renin and angiotensin by infection of endothelial and renal cells (rather than induction of plaques?) and induction of cytokines. Importantly, the cytokine-enhancing effects were restricted to CMV-infected cells only.

Although the findings are very suggestive of a causal relationship, it remains to be proven whether hypertension via enhanced extrarenal production of renin and angiotensin is the causal factor of CMV-associated cardiovascular disease in the normal human situation. Some statements are not underpinned by the current data. See for instance the blue marked text in the author’s conclusion.


Arterial wall depicting major inflammatory features common to CMV infection and atherosclerosis. – K. Froberg

The current prevailing hypothesis is that atherogenesis is an inflammatory response to acute or chronic endothelial injury. Possible causes for this endothelial injury include free radicals, modified LDL, hypertension, diabetes mellitus and smoking [4,5]. More recently CMV and other infections have been added to the list of risk factors. It is generally thought that the formation of plaques concurrent with the enhanced induction of cytokines can contribute to atherosclerosis and vascular disease, after many years of chronic, active inflammation of the arterial wall.

In the present model, atherosclerosis was only observed in 3 out of 12 HD-V mice. This indicates that atherosclerosis is not involved in the increase of blood pressure. Instead, the present study shows, that CMV might contribute to cardiovascular disease via an effect on blood pressure, presumably mediated through an enhanced expression of renin and Ang II.

With regard to the statistical analysis, I wonder why each virus-treated group was only compared to its mock-infected control (using the Student’s t-test)? Why weren’t all groups compared to each other, using another statistical test? Is this because another approach would have rendered most differences insignificant? The differences between groups are consistent but not very large and the standard deviations are quite overlapping. (Thus significance might be lost when more rigid test are used)

It would for instance be interesting to know the relative contribution of the fatty diet to the rise in blood pressure, or the risk in the 4 groups relative to each other.
We all have CMV (well about 70-90%), but just few of us get high blood pressure (at young age). So likely other factors come into play, that may enhance the detrimental effects of CMV or vice versa. Therefore, it would for instance be interesting to know, to which extent high fat consumption would contribute to high blood pressure as well. Is the suggested order as we see it real: V alone giving slight elevation of blood pressure, HD alone giving more elevation and VHD giving the highest rise? (2×2 table).

The study has some fascinating results, but it is too soon to think about antiviral treatment as the authors and media [3] suggest. Nor is it necessary to worry the public by stating that: You can find out if you have been infected with CMV by requesting a blood test from your GP”, as the daily mail does. This is useless, because CMV is omnipresent.

It hardly seems to be justified to suggest that everybody should be treated with antivirals. And what about the other viruses or bacteria that may play a role? Furthermore, lifestyle and other (immunological) parameters may be more important ànd lifestyle changes may be easier to implement.

Update: Tuesday 2009-05-26: 17.30 pm.

HATTIP: @microbytes (Twitter)

Figure: Kent Froberg from the University of Minesota (


  1. Cheng, J., Ke, Q., Jin, Z., Wang, H., Kocher, O., Morgan, J., Zhang, J., & Crumpacker, C. (2009). Cytomegalovirus Infection Causes an Increase of Arterial Blood Pressure PLoS Pathogens, 5 (5) DOI: 10.1371/journal.ppat.1000427
  4. Many reviews from Cathrien A. Bruggeman and colleagues, like this review in a Book.
  5. Kent Froberg from the University of Minesota (
Human Herpesvirus 5 (HHV-5)