Calorie Control Council Response to a Sucralose Study by Abou-Donia, et al.

Posted by & filed under Health Professionals, Statements, Sucralose.

ATLANTA (September 23, 2008) — The Calorie Control Council takes this opportunity to respond to some of the points discussed in the study by Abou-Donia, et al. recently published in the Journal of Toxicology and Environmental Health Part A.  The study alleges that SPLENDA® No Calorie Sweetener, Granular, (which contains a combination of maltodextrin and sucralose) will adversely affect gut health and may interfere with the absorption of certain drugs and nutrients. However, this small study is contradictory to the scientific literature showing that sucralose is safe and does not cause adverse affects.  It is important for consumers and health professionals to understand the following in relation to this study and SPLENDA® Granulated Sweetener:

  1. The methodology of the study by Abou-Donia et al. has many flaws, including a lack of proper control groups.  The control group consumed plain water, which does not provide an applicable means of metabolic comparison.  The control group’s diet contained no sucralose or carbohydrate (e.g., maltodextrin) and therefore does not serve as a useful means of comparison.
  2. Studies conducted on sucralose in both humans and animals show absorption of sucralose in the gut is limited and the majority is excreted unchanged.  In fact, at the end of the 12 week treatment period in the Abou-Donia et al. study, the animals had no observable health effects.  Thus, there is no reason to believe that sucralose would adversely affect gut health.  Long term ingestion studies of sucralose have shown no adverse side effects, metabolic or otherwise.
  3. Sucralose is not metabolized by the body for energy.  Most is not absorbed and thus excreted unchanged, without accumulation in the gut or elsewhere in the body.  As a result, there is no reason that sucralose would cause poor nutrient or drug absorption.  Further, the test dosage given in the study by Abou-Donia et al. contained 93.6 percent maltodextrin (a carbohydrate) and only 1.1 percent sucralose thus, it would be unlikely that any reported metabolic effects could be attributed to pure sucralose.
  4. Clinical studies support that sucralose has no side effects.  Sucralose was administered to both healthy subjects and people with diabetes, in quantities well in excess of typical exposure levels, with no adverse consequences.  In studies of people with diabetes, changes in diabetes treatment (drug therapy) regimens were also monitored.  There were no significant differences found between subjects exposed for months to daily high amounts of sucralose and subjects who received placebo over the same time period.
  5. The study does not support a dose response relationship.  A significant change in body weight was seen with the low dose sucralose intake (100 mg/kg/d in water) but not in the high (300 and 500 mg/kg/d in water) or highest dose groups (1000 mg/kg/d in water).  The control group also gained weight.  Further, there was no attempt to control for or measure overall food and calorie intake and such intake was not reported.
  6. The researchers report a decrease in beneficial gut bacteria with the consumption of sucralose treatment.  In actuality, both the good and bad bacteria decreased, indicating a natural fluctuation on bacterial levels. When determining the effect on bacterial levels, it is the ratio that matters and not the individual bacterial response.

Importantly, sucralose has been available internationally for over 15 years, and has been used safely by millions of people.  Moreover, studies show that no-calorie sweeteners, including sucralose, can be useful tools for calorie management, which is a common concern in optimally managing one’s health.

An overwhelming body of science supports the fact that sucralose has an excellent safety profile and is well-tested. The safety of sucralose is supported by more than 100 scientific studies conducted over a 20-year period.  The safety of sucralose has been confirmed by leading medical, scientific and regulatory authorities around the world including, the US Food and Drug Administration (FDA), the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA), European Commission’s Scientific Committee on Food, Health Canada and Food Standards Australia/New Zealand.  For more information about sucralose, visit: www.sucralose.org.

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Study on Artificially Sweetened Beverages and Preterm Delivery Is Misleading

Posted by & filed under Pregnancy, Statements.

ATLANTA (August 30, 2008) — Findings presented in “Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study” are weak and misleading.

The Calorie Control Council cites the following as serious limitations of the study:

  • No true association between the intake of artificially sweetened beverages and preterm delivery was found, although the authors reported the contrary. The relationship presented between the consumption of artificially sweetened beverages and preterm delivery was extremely weak. Further, the authors misinterpreted the statistics, stating that the association found was small but significant, when in fact it was on the edge and not what statisticians would consider to be significant. (i.e. – The confidence interval (CI) should not include 1 to be able to consider a finding significant.)
  • The association between the intake of artificially sweetened beverages and preterm delivery was due to other factors, not low calorie sweeteners. The relationship presented between the consumption of artificially sweetened beverages and preterm delivery was extremely weak, and when other factors such as age, history of preterm delivery and sugar-sweetened beverage intake were controlled for, the relationships in most categories were no longer statistically significant. This suggests that other factors are responsible for the increased risk of preterm delivery, not artificial sweeteners.
  • The results of the study do not seem to be biologically plausible. It is peculiar that the risk of preterm delivery reported by the authors was only increased in the late preterm delivery group, but not in the moderate or early preterm group. Intuitively, one would think that if there was a risk, it would be more likely to affect the more vulnerable group. Further, it does not seem logical that women consuming 1-6 servings of sugar-sweetened beverages per day would have a lower risk of early preterm delivery than those consuming more than 4 servings/day or less than one serving/week as the authors reported.
  • Other factors may have influenced the findings. The authors controlled for some things known to impact the risk of preterm delivery, but admitted there might be other factors for which they did not control. For example, the study did not control for other dietary habits or socioeconomic status, both of which may have influenced preterm delivery risk.
  • The study cannot determine cause and effect. Finally, because the study was observational, it is impossible to ascertain if the artificially sweetened beverages were the cause of any of the findings seen. Even the authors said other variables could be influencing the results. Variables such as additional dietary factors, socioeconomic factors or other factors that increase the risk of premature births (e.g. – certain infections, high blood pressure, clotting disorders, bleeding, certain birth defects in the baby, being pregnant with a single fetus that is the result of in vitro fertilization, anemia, stress, depression, lack of support, etc.) were not considered by the authors and could have had an effect.
  • The study had numerous limitations. The authors noted several limitations of the study: 1) study subjects could have incorrectly reported what they ate; 2) study subjects do not necessarily represent everyone in Norway, much less other parts of the world; 3) factors other than the ones for which researchers controlled could have affected the relationship.

The use of low-calorie sweeteners in pregnancy has been well studied both in humans and in animals. Before approving the currently available low-calorie sweeteners, regulatory bodies world-wide determined that the low-calorie sweeteners are safe for all populations, including special groups such as the elderly, children, and pregnant and nursing women. Further, leading health groups such as the Academy of Nutrition and Dietetics and American Diabetes Association support the safe use of low-calorie sweeteners during pregnancy.

Importantly, in 2011 both the European Food Safety Authority (EFSA) and the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) confirmed that low calorie sweeteners are safe for pregnant women. Additionally, in 2011, EFSA concluded that there was no available evidence to show that consumption of artificially sweetened soft drinks led to preterm delivery.

Calorie Control Council Response to Thuy et al

Posted by & filed under Fructose, Health Professionals, Research Summaries.

Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake

Thuy S, Ladurner R, Volynets V, Wagner S, Strahl S, Konigsrainer A, Maier KP, Bischoff SC, Bergheim I. Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. J Nutr. 2008 Aug;138:1452-5.

Background
This article is a collaboration of three German laboratories: Department of Nutritional Medicine, University of Hohenheim, Stuttgart; Department of General, Visceral and Transplant Surgery, Tübingen University Hospital; and Liver Center, City Hospital, Esslingen. The purpose of the study is to better understand the biochemical and pathological changes associated with the development of nonalcoholic fatty liver disease (NAFLD) so that improved therapies can be developed

Author Justification
High dietary carbohydrate intake is claimed to be a key factor in the development of NAFLD, increasing the odds of later stages of the disease. In animal studies, fructose at levels up to 60% of calories is reported to increase lipid accumulation in the liver leading to insulin resistance, elevated plasma triglycerides and oxidative stress. The authors previously reported that moderate fructose consumption in mice could lead to increased intestinal translocation of bacterial endotoxin, induction of hepatic tumor necrosis factor alpha and subsequent liver steatosis 1 (1). Simultaneous treatment with antibiotics almost completely blocked the effect of fructose on mouse liver

Aim
Assess dietary intake, endotoxin and PAI-1 concentration of NAFLD patients and controls to further investigate the mechanisms involved in the development of NAFLD in humans.

Experimental Design
The dietary intakes of 12 NAFLD patients and 6 control subjects were assessed. Measurements of several biochemical markers of NAFLD were made: plasma endotoxin and plasminogen activator inhibitor (PAI)-1, hepatic PAI-1 and toll-like receptor (TRL) 4 mRNA.

Results

  • Fructose intake, endotoxin and PAI-1 concentration increased in NAFLD patients;
  • Endotoxin and PAI-1 concentration are related;
  • Carbohydrate intake and PAI-1 concentration are related

 

Author Conclusions

  1. Endotoxin and its receptor TLR4 and plasma PAI-1 concentration, dietary fructose intake and PAI-1 are associated with NAFLD in humans
  2. Hepatic TLR4 expression, plasma PAI-1 and endotoxin concentrations are related
  3. Hepatic PAI-1 expression might be related to total carbohydrate and sugar intake.
  4. Results are consistent with the concept that intestinal permeability and flora, as well as dietary pattern [read ‘fructose intake’] and PAI-1, are important in the pathogenesis of NAFLD in humans.
  5. Further studies are needed to explore the molecular mechanisms responsible

 

Critique

  • In the authors’ previous paper (1), mice were given ad libitum water; water + artificial sweetener (cyclamate, Sunett and saccharin); or 30% aqueous solutions of glucose, sucrose or fructose. It appears from examination of the data that the mice took in approximately 55% of calories as fructose, comparable to the level (60-65%) commonly used to induce metabolic abnormalities in rats (see ex., RJ Johnson). The upsets attributed to fructose clearly are inappropriate as extrapolated to humans, due to the exaggerated exposures, single-sugar protocol and mouse-human differences.
  • The link between fructose intake and NAFLD in the current paper is very weak:
    • Fructose intakes were teased from patient dietary recall of recent meals during nutritionist interviews, a widely acknowledged imprecise method.
    • The difference in total fructose (free + sucrose) intake between NAFLD patients and controls was about 10 g/d = 40 kcal/d. The average daily calorie intake between the two groups was about 2200 kcal. Thus, NAFLD patients took in an extra 1.8% of calories as fructose; a rather modest difference.
    • The difference in sucrose intake between patients and controls was about 9 g/d = 36 kcal. NAFLD patients took in an extra 1.6% of calories as sucrose; not much less than the fructose variable
  • That fructose, but not sucrose, differences were statistically significant may be attributable to the low numbers of subjects (12 NAFLD; 6 control). Statisticians would consider this study to have low statistical power, which earns it low credibility in the long run

 

References
1. Bergheim I, Weber S, Vos M, et al. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol 2008;48:983-92.

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Calorie Calorie Control Council Response to Parks et al

Posted by & filed under Uncategorized.

Dietary sugars stimulate fatty acid synthesis in adult

Parks EJ, Skokan LE, Timlin MT, Dingfelder CS.
J Nutr. 2008 Jun;138:1039-46

 

Background
This study comes out of the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas (author Parks); Department of Biomedical Engineering, University of Texas at Arlington (Skokan); and Department of Food Science and Nutrition, University of Minnesota, St. Paul (Timlin & Dingfelder).

Hypothesis
The authors hypothesized that a fructose-induced rise in lipogenesis (fat production) in the morning would further increase triglyceride (TG) concentrations after the next meal

Justifications

  • Fructose has been used in controlled over-feeding studies to elevate daylong serum triglyceride concentrations in healthy and diabetic subjects;
  • Elevated TG could lead to an accumulation of lipoprotein remnants, which could be atherogenic;
  • The natural pattern of blood TG is diurnal (occurring during the day), rising throughout the day and peaking around midnight.

Experimental Design
Human subjects consumed a carbohydrate bolus (single large dose) of sugars (85 g each) in a random and blinded order, followed by a standardized lunch 4 h later. Carbohydrate boluses consisted of glucose (100G:0F), a mixture of 50G:50F glucose:fructose or a mixture of 25G:75F glucose:fructose.

Author Conclusions

  • Lipogenesis (lipid synthesis) was stimulated for all treatments, but it was nearly double after the 50G:50F and 25G:75F treatments compared to the 100G:0F treatment.
  • An early stimulation of lipogenesis after fructose, administered in a mixture of sugars, augments subsequent postprandial (after a meal) lipemia (excess lipids in the blood).
  • Acute intake of fructose stimulates lipogenesis and may create a metabolic milieu that enhances esterification of fatty acids flowing to the liver to elevate postprandial TG synthesis.

 

Critique

  • Administration of test carbohydrates by bolus in the absence of other dietary nutrients is not representative of the way humans take in sugars. Humans typically eat complex meals consisting of protein, fat and carbohydrate together. Bolus administration would be expected to give exaggerated results
  • To their credit the authors do compare various glucose:fructose blends, however some of the data (Table 2) are inconsistent: It is puzzling that there is so little difference in morning fractional and absolute lipogenesis, and in post lunch triglycerides between 50G:50F and 25G:75F variables. There also is little distinction between these variables for total glucose, total insulin and fatty acids. This is at odds with historical data, which show distinct, titratable differences in metabolic parameters vs. fructose dose.
  • Though the experiment is presented as being more representative of real life – ie, the bolus is presented as mixed sugars – it is actually quite high in fructose. When fructose calories from the morning bolus are summed with those from lunch (Table 1), the 50G:50F variable received 22% of calories as fructose, while the 25G:75F variable received 29% of calories as fructose – two and three times the typical dietary exposure in just two meals. Thus, a health risk for the general public should NOT be generated from these data.
  • The authors acknowledged that the 100G:0F bolus stimulated a lower rise in lipogenesis in the current study (8%) than in their previous study (23%). The peak in lipogenesis after both fructose treatments (50:50 and 25:75) was 17% — twice the glucose treatment in the current study, but substantially lower than the previous one. The magnitude of the lipogenesis seems somewhat dependent on whether the sugars delivery solution also contains fat and protein (observation made in comparing present with higher TG levels in past experiment). Fat and protein were absent in the present study, resulting in fewer calories fed. It is not above researchers to manipulate protein and fat to produce favorable results. It matters a great deal whether the current or previous glucose control value is correct: viewed against the current value, fructose appears to have an effect; viewed against the previous value, fructose has no unique effect on lipogenesis. This seems a serious inconsistency and the results must be discounted until one or the other glucose value is validated.
  • Human metabolism can be rather simplistically viewed as a factory with many assembly lines producing many possible products. It seems reasonable that if one assembly line is primed more with raw materials than another, it will be able to make product faster. It also seems reasonable that if the assembly lines are shut down for a period of time (between the bolus and lunch), the one best primed at the next startup (lunch) will begin making product the fastest. This is, in essence, what Parks has done. With an exaggerated bolus of fructose, she has primed the fructose-to-lipid pathway – a more focused and direct route to lipids than the glucose-to-lipid pathway, which has more controls and more optional pathways.
  • Finally, the small sample size — only six subjects — is another significant limitation. Because of the admitted “metabolic flexibility” of human metabolism (last line, p.1044), individual variations in lipogenesis rates with different sugars blends could appreciably skew experimental results in so small a sample size.

The post Calorie Calorie Control Council Response to Parks et al appeared first on FructoseFacts.

Calorie Calorie Control Council Response to Parks et al

Posted by & filed under Fructose, Health Professionals, Research Summaries.

Dietary sugars stimulate fatty acid synthesis in adult

Parks EJ, Skokan LE, Timlin MT, Dingfelder CS.
J Nutr. 2008 Jun;138:1039-46

 

Background
This study comes out of the Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas (author Parks); Department of Biomedical Engineering, University of Texas at Arlington (Skokan); and Department of Food Science and Nutrition, University of Minnesota, St. Paul (Timlin & Dingfelder).

Hypothesis
The authors hypothesized that a fructose-induced rise in lipogenesis (fat production) in the morning would further increase triglyceride (TG) concentrations after the next meal

Justifications

  • Fructose has been used in controlled over-feeding studies to elevate daylong serum triglyceride concentrations in healthy and diabetic subjects;
  • Elevated TG could lead to an accumulation of lipoprotein remnants, which could be atherogenic;
  • The natural pattern of blood TG is diurnal (occurring during the day), rising throughout the day and peaking around midnight.

Experimental Design
Human subjects consumed a carbohydrate bolus (single large dose) of sugars (85 g each) in a random and blinded order, followed by a standardized lunch 4 h later. Carbohydrate boluses consisted of glucose (100G:0F), a mixture of 50G:50F glucose:fructose or a mixture of 25G:75F glucose:fructose.

Author Conclusions

  • Lipogenesis (lipid synthesis) was stimulated for all treatments, but it was nearly double after the 50G:50F and 25G:75F treatments compared to the 100G:0F treatment.
  • An early stimulation of lipogenesis after fructose, administered in a mixture of sugars, augments subsequent postprandial (after a meal) lipemia (excess lipids in the blood).
  • Acute intake of fructose stimulates lipogenesis and may create a metabolic milieu that enhances esterification of fatty acids flowing to the liver to elevate postprandial TG synthesis.

 

Critique

  • Administration of test carbohydrates by bolus in the absence of other dietary nutrients is not representative of the way humans take in sugars. Humans typically eat complex meals consisting of protein, fat and carbohydrate together. Bolus administration would be expected to give exaggerated results
  • To their credit the authors do compare various glucose:fructose blends, however some of the data (Table 2) are inconsistent: It is puzzling that there is so little difference in morning fractional and absolute lipogenesis, and in post lunch triglycerides between 50G:50F and 25G:75F variables. There also is little distinction between these variables for total glucose, total insulin and fatty acids. This is at odds with historical data, which show distinct, titratable differences in metabolic parameters vs. fructose dose.
  • Though the experiment is presented as being more representative of real life – ie, the bolus is presented as mixed sugars – it is actually quite high in fructose. When fructose calories from the morning bolus are summed with those from lunch (Table 1), the 50G:50F variable received 22% of calories as fructose, while the 25G:75F variable received 29% of calories as fructose – two and three times the typical dietary exposure in just two meals. Thus, a health risk for the general public should NOT be generated from these data.
  • The authors acknowledged that the 100G:0F bolus stimulated a lower rise in lipogenesis in the current study (8%) than in their previous study (23%). The peak in lipogenesis after both fructose treatments (50:50 and 25:75) was 17% — twice the glucose treatment in the current study, but substantially lower than the previous one. The magnitude of the lipogenesis seems somewhat dependent on whether the sugars delivery solution also contains fat and protein (observation made in comparing present with higher TG levels in past experiment). Fat and protein were absent in the present study, resulting in fewer calories fed. It is not above researchers to manipulate protein and fat to produce favorable results. It matters a great deal whether the current or previous glucose control value is correct: viewed against the current value, fructose appears to have an effect; viewed against the previous value, fructose has no unique effect on lipogenesis. This seems a serious inconsistency and the results must be discounted until one or the other glucose value is validated.
  • Human metabolism can be rather simplistically viewed as a factory with many assembly lines producing many possible products. It seems reasonable that if one assembly line is primed more with raw materials than another, it will be able to make product faster. It also seems reasonable that if the assembly lines are shut down for a period of time (between the bolus and lunch), the one best primed at the next startup (lunch) will begin making product the fastest. This is, in essence, what Parks has done. With an exaggerated bolus of fructose, she has primed the fructose-to-lipid pathway – a more focused and direct route to lipids than the glucose-to-lipid pathway, which has more controls and more optional pathways.
  • Finally, the small sample size — only six subjects — is another significant limitation. Because of the admitted “metabolic flexibility” of human metabolism (last line, p.1044), individual variations in lipogenesis rates with different sugars blends could appreciably skew experimental results in so small a sample size.

The post Calorie Calorie Control Council Response to Parks et al appeared first on FructoseFacts.

Calorie Control Council Response to Couchepin et al

Posted by & filed under Fructose, Health Professionals, Research Summaries.

Markedly Blunted Metabolic Effects of Fructose in Healthy Young Female Subjects Compared with Male Subjects

Couchepin C, Le KA, Bortolotti M, da Encarnacao JA, Oboni JB, Tran C, Schneiter P, Tappy L. Diabetes Care. 2008 Jun;31:1254-6.

 

Background
This study originates from the Department of Physiology, Lausanne University School of Biology and Medicine, Lausanne, Switzerland in the laboratory of Luc Tappy.

Hypothesis
The effects of short-term fructose overfeeding on fasting lipid metabolism and insulin sensitivity in human subjects may be sex-dependent.

Justifications

  • High fructose intake has been associated with adverse metabolic effects (1).
  • Several reports show in rats that fructose has a more pronounced adverse metabolic effect in males than females.
  • In humans, only males show fructose-induced hypertriglyceridemia.

Author Conclusions

  • Fructose overfeeding increased fasting triglyceride concentrations by 71 vs. 16% in male vs. female subjects, respectively.
  • The following metabolic markers were increased after fructose over-feeding in male subjects: endogenous glucose production (+12%), alanine aminotransferase (+38%), and fasting insulin (+14%). Fasting plasma free fatty acids and lipid oxidation were inhibited in males. All markers were not significantly affected by fructose in female subjects.
  • Short-term fructose overfeeding produces hypertriglyceridemia and hepatic insulin resistance in men, but these effects are markedly blunted in healthy young women.

Critique

  • Contraceptive hormones are well known to influence metabolic processes and women who are hormonally active are often barred from such studies. By allowing women on hormonal contraception to participate in the study, the authors have added a level of complexity to the data analysis.

This is a rare paper in which the authors admit that they feeding an excess of fructose to the study subjects – the term overfeeding is used several times in the paper. The isocaloric diet, with an advertised 10% mono and disaccharides might be expected to contribute 100 cal in the form of fructose. The overfeeding is accomplished by supplementing test subjects with 3.5 g fructose/kg fat-free mass/day — this contributes about 843 cal for males and 735 cal for females. Fructose supplementation in this paper thus contributes about 32% of total calories for men and 29% for women, nearly fourtimes the amount consumed by the typical adult and nearly twice the amount consumed by the 90-percentile of sweetener users (2)

References
1. Havel PJ. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev. 2005 May;63:133-57.
2. Park YK, Yetley EA. Intakes and food sources of fructose in the United States. Am J Clin Nutr. 1993 Nov;58:737S-47S.

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