Two journal articles appeared on my laptop in the past few weeks. Science moves us forward. It is not a clean process. It is not always clear. In an age that calls out for certainty, we look to science to save us. Science is an uncertain enterprise. It is like a jigsaw puzzle with many pieces. Some of these pieces fit into a useful pattern. Others are useless and slated for discard. Imagine a 400-piece puzzle with 1000 pieces in the box! How do we decide which 600 to toss?
Technology helps move scientific findings into both useful and destructive gadgets. I taught a course in “Food Research and the Scientific Method.” Major topics included critical thinking skills and critical evaluation of the scientific literature. I describe my approach in Becoming a Food Scientist. Today I use those skills to analyze those two journal articles.
A hamburger in Israel
Recent news reports suggest that junk (aka ultra-processed) foods compromised bone health. Parents should avoid feeding ultra-processed foods to their children. The original article (1) appeared in the scientific journal Bone Research. This study was different. It did not mine vast databases to correlate between diseases and ultra-processed food. This study looked at defined diets and bone quality. At last, some real data. That was until I took a closer at the original article.
Objective: to examine “the effect of an unbalanced ultra-processed diet (UPF) during postnatal growth on skeletal development and quality.”
Methods: Researchers divided 16 young rats into two equal groups. One group received a standard diet and the other an ultra-processed one. The UPF diet consisted of a “roll, hamburger, tomatoes, lettuce, ketchup (without onion or pickles) and French fries.” Added to it was a typical soft drink (CSD). The whole meal was homogenized, shaped into patties, and frozen. There were other experiments looking at the effects of macronutrients, micronutrients, and eating patterns.
Results: “Taken together, these results demonstrated the deterioration in the structural and mechanical features of bones from the UPF + CSD vs. Control group.” Effects showed up within six weeks of the experiment. Researchers noted that chemical analysis of the UPF + CSD diet was low in calcium (Ca) and phosphorous (P). The micronutrient experiments added in calcium and phosphorous equal to amounts in the Control diets. The added Ca/P led to more severe bone damage than the UPF + CSD diet. They explained this result by the presence of phosphoric acid in the soft drink. Phosphoric acid binds calcium and has been suggested as a major reason for avoiding soft drinks.
Conclusions: “Our findings highlight, for the first time, the severe impact of consuming ultra-processed foods on the growing skeleton.”
Critical evaluation. First, it was a fast-food diet and not a true ultra-processed diet. Only the soft drink, roll, ketchup, and French fries were ultra-processed. Four ultra-processed foods do not qualify as representative of ultra-processed foods which comprise 60% of the American diet. Second, there was no cheese with the burgers. It is difficult to get a cheeseburger in Israel due to kosher dietary restrictions. What would the results have been if cheese had been part of the UPF + CSD diet? I suspect that the phosphoric acid bound the calcium during homogenization before freezing in the micronutrient experiments. The most recent meta-analysis suggests that lack of milk consumption rather than the ingestion of phosphoric acid is the major cause of fractures in children (2). This meta-analysis also emphasizes the importance of vitamin D in bone health. Vitamin D was not mentioned in the Israeli article, but it is found in dairy products.
My assessment: The diet is not representative of ultra-processed foods. The conclusion generalizes beyond its results. Lack of cheese in the diet and an inability to control for vitamin D invalidates the study in my mind.
The previous article was a study. The next one is a review. Studies deal with real data around a narrow objective. The authors interpret that data in the context of the published literature in that narrow field. Reviews place a topic in a broader context. The best reviews do not advocate a particular position. Rather, they point out positive and negative aspects of prevailing views. Both studies and reviews are needed to advance a scientific field. Without studies, we would have no reviews. Without reviews, studies would have little or no broader context.
Blocking Fructose to improve health
Fructose is a very controversial molecule found in food. High-fructose corn syrup (HFCS) has risen to the top of the list of badadditives. NOVA gives fructose its blessing when half of the sucrose molecule if added at home. Table sugar is a culinary ingredient. It is also OK in honey, maple syrup, or agave syrup (90% fructose). Only when adding HFCS or sucrose to a processed product in a manufacturing plant does fructose become dangerous. A review in Advances in Nutrition (3) presents a different perspective. Below are the major points made in the review.
Major premises. Obesity and metabolic syndrome are serious illnesses facing the American public. Diet is only one of many factors leading to these conditions. Sugary beverages sweetened with HFCS are major contributors to these conditions. Fructose affects metabolism beyond its caloric value. Metabolized by the liver, fructose lowers the effect of leptin. Leptin is a hormone that suppresses appetite. Epidemics of obesity, diabetes, and metabolic syndrome increased in the country in recent years. Fructose played a major role in that increase.
Historical perspective. In 1893, Sir William Osler published the Principles and Practice of Medicine. He predicted that the significant diseases of the 20th Century would be non-communicable. Among those diseases were corpulence (obesity) and elevated pulse tension (high blood pressure). Also mentioned were lean (type 1) and obese (type 2) diabetes as well as angina.
Beginning of the epidemics. Obesity and diabetes showed dramatic increases in the early part of the century. A debate arose between sugar consumption and overnutrition as the major cause.
Mechanisms driving obesity and diabetes. Birds and humans compensate for fluctuations in weight when overfed or underfed. Release of the hormone leptin signals satiety. Obese subjects exhibit leptin resistance leading to overeating and no weight compensation. Other hormonal responses lead to impaired regulation of food intake. Lack of physical activity may make the situation worse. Fructose affects ATP concentrations and induces mitochondrial stress. Obesity leads to decreased fatty-acid oxidation in the liver, muscle, and fat cells. Investigators associate such activities with overeating and lower physical activity. Other studies implicate hormonal and sensory factors stimulated by marketing of energy-dense foods. Underlying biological factors comprise a potential paradigm to replace the current energy-balance theory.
Fructose as a driver of fat storage: “[F]ructose increases energy intake, reduces insulin sensitivity, increases circulating TGs [triglycerides] and visceral fat stores, reduces fat oxidation, and reduces energy metabolism compared with other foods such as glucose or starch.” Fructose also entices us to overeat energy-dense foods.
Sugar consumption related to incidence of obesity and diabetes. Increases in obesity and diabetes started to rise in the late 70s and early 80s. HFCS was first added to replace sugar in sugar-sweetened beverages and other processed foods about the same time. HFCS consumption peaked in 1999 and is declining in the USA. Obesity appears to be leveling off since then.
Limitations of the article. The authors acknowledge some limitations to their theory. Not all studies in the literature support the theory that fructose contributes more to obesity than through its calories. Other factors may contribute as much to weight regulation as fructose. These factors include “genetics, epigenetics and fetal programming, and development of fatty liver.” Natural fruits contain fructose, but the effect is reduced to the presence of dietary fiber. Fruit juices contain little fiber and much fructose, contributing to the problem.
Conflicts of interest. A feature introduced to journal articles is in recent years is a statement of conflict of interest. Turns out that authors Johnson and Lanaspa have patents out on fructose blockers. They have also started a company with Sanchez-Lozada to develop inhibitors for fructose metabolism. As such, they stand to gain financial rewards if their theory is adopted.
My assessment: Unlike most of the ultra-processed studies, the authors propose a mechanism that is testable. Blame focuses on one molecule–fructose. The conflict of interest by the authors is disturbing. I commend the journal for pointing it out, but why did they accept the manuscript for publication? I expect that a senior scientist from a cola company would not be able to publish an alternate view. If sugars lead to diabetes, why don’t the cohort studies separate out those products from ultra-processed food?
The authors associate the rise in obesity in the US with the introduction of HFCS into sugared soda. They state that HFCS is liquid and replaced solid sugar. My understanding is that invert sugar, also a liquid sweetener, was used in most soft drinks before the introduction of HFCS. An enzymatic process converts sucrose to invert sugar. It contains 50% glucose and 50% fructose. Corn syrup is almost all glucose. An enzymatic process converts corn syrup to high fructose corn syrup. HFCS-55 is the sweetener of choice for soft drinks. Thus HFCS is 55% fructose and 45% glucose. In the early 80s, diet drinks emerged in the market lowering consumption of sugared sodas. The increase of fructose in the American food supply is not as great as the authors would have us believe.
Bottom line: Did the journalists actually read the original study on hamburgers in Israel? Did any nutrition scientist review the article before publication? Are only negative articles on processed food free from conflicts of interest? Is the problem with ultra-processed food one of a single additive like HFCS? Or is it a problem with all food additives as purported in ultra-processed foods as classified by NOVA? Which jigsaw puzzle pieces do we keep? Which ones do we discard? These articles .generate more questions in my mind than answers.
BTW, have you seen my guest editorial on defending processed food on the IFT website?
Next week: Food in the news as we emerge from the pandemic
(1) Zaretsky, J., S. Greiss-Fishheimer, A. Carmi, T.T. Schmul, L. Ofer, T. Sinai, S. Penn, R. Shahar, and E. Monsonego-Ornan, 2021. Ultra-processed food targets bone quality via endochondrial ossification. Bone Research 9:14. https://doi.org/10.1038/s41413-020-00127-9
(2) Handel, M.N., B.L. Heitmann and B. Abrahamsen, 2015. Nutrient and food intakes in early life and risk of childhood fractures: a systematic review and meta-analysis. American Journal of Clinical Nutrition 102:1182-1195. https://doi.org/10.3945/ajcn.115.108456
(3) Johnson, R.J., L.G. Sanchez-Lozada, P. Andrews and M.A. Lanaspa, 2017. Perspective: A historical and scientific perspective of sugar and its relation with obesity and diabetes. Advances in Nutrition 8(3):412-422 https://doi.org/10.3945/an.116.014654