DeChristopher LR, Tucker KL. Excess free fructose, high-fructose corn syrup and adult asthma: the Framingham Offspring Cohort. Br J Nutr. 2018;119(10):1157-1167.
Retrospective cohort study
Participants were part of The Framingham Offspring Cohort, a prospective study of offspring (n=5,013) of the original Framingham Cohort. Participants were adult, predominantly non-Hispanic white men and women, with a mean age of 47.9 years; at baseline 39% were overweight and 17% were obese.
Participants completed food frequency questionnaires starting in 1984 as part of the Framingham study. The data gathered between 1984 and 2001 is of particular interest as this period of approximately 17 years is when high-fructose foods were first introduced and became common in the US diet; soft drink producers shifted from using sucrose to HFCS as a sweetener in 1984. Data from 2,692 of the participants was complete enough to be included in the analysis.
Study Parameters Assessed
Information regarding the intake of high-fructose corn syrup (HFCS), HFCS-sweetened soda, fruit drinks, and apple juice were gathered from the food frequency questionnaires, and the incidence of asthma was based on participants’ self-report as recorded in the Framingham data. Consumption of diet soda and orange juice—a 100% juice with a 1:1 fructose to glucose ratio—was included for comparison.
Primary Outcome Measure
Cox proportional hazards models were used to assess associations between consumption of sweetened soda, fruit juice, and fruit drink with self-reported incident asthma.
Increasing intake of any combination of HFCS-sweetened soda, fruit drinks, and apple juice was significantly associated with progressively higher asthma risk, plateauing at 5-7 times/week consumption vs never/seldom consumption, independent of potential confounders (hazard ratio [HR]: 1.91; P<0.001). “About once a day”–consumers of HFCS-sweetened soda had a 49% higher risk (P<0.011), moderate apple juice consumers (2-4 times/week) had a 61% higher risk (P<0.007), and moderate fruit drink consumers had a 58% higher risk (P<0.009), compared with never/seldom consumers. There were no associations of diet soda or orange juice consumption with asthma incidence.
At this point the evidence that excess fructose consumption is linked to asthma is strong enough that this should be on our radar whenever we see a child or adult patient with asthma.
Evidence that fructose consumption is associated with asthma has been growing over that past few years.1-4
The authors of this current study reported in 2016 that intake of high-fructose beverages including apple juice, fruit drinks and soda was associated with increased risk of asthma in children (aged 2-9 years).4
For the moment probably the most important thing we can do for our patients is to help them recognize sources of fructose in their diet, and to help them understand that fructose is no longer considered the “healthy sugar” it once was.
There is also evidence that a woman’s fructose consumption during pregnancy is associated with an increased risk of asthma in her offspring.5 A study by Wright et al published in February 2018 examined associations between maternal and child consumption patterns with current asthma in mid-childhood, in participants of Project Viva, a prospective pre-birth cohort of 1,068 mother-child pairs. Higher maternal pregnancy intake of fructose (odds ratio [OR]: 1.58; 95% confidence interval [CI]: 0.98-2.53) was associated with greater risk of mid-childhood asthma.6
In a 2013 epidemiological study by the US Centers for Disease Control and Prevention (CDC), Park et al reported that US high school students (n=15,960) who regularly consumed HFCS-sweetened soda were 64% more likely to have asthma than those who avoided consumption.7
Initially it was theorized that the asthma might be triggered by preservatives in these beverages, but as no association has been seen in diet beverages that contain similar chemical burdens, this theory is now discounted.8
It appears that the ratio of fructose to glucose is an important predictor of asthma risk. Orange juice with a 1:1 ratio of fructose-to-glucose has not been associated with asthma. Nor has apple juice, which is also close to 1:1.
The highest increase in asthma risk (91%) was seen among participants who consumed a beverage containing added fructose about once per day (5-7 times/week). Even moderate consumers (2-4 times/week) were at significantly increased risk (61% higher than never/seldom consumers).
Interestingly, consuming high-fructose beverages more than once per day seemed to be less of a problem, increasing risk by only 49%. The authors suggest that this may be the result of some increasing immune tolerance with higher exposure. They admit that they may be underestimating the effect of fructose in the diet. National data suggest that the average American now consumes about 24 pounds of HFCS per year, or 30 grams per day.9
It’s not just asthma that is linked to fructose. The authors of the current study reported back in 2015 a significant positive association between consumption of HFCS-sweetened soda and chronic bronchitis in adults.10
The authors of this study suggest it is excess free fructose in the diet that is the culprit. Fructose and glucose together in a 1:1 ratio as found in sucrose do not appear to cause a problem. High dietary fructose comes from high fructose corn syrup (HFCS), agave syrup, crystalline fructose, apple juice, and combinations of fruit juice concentrates, none of which humans have evolved consuming in significant quantities. The list of foods that naturally contain high fructose to glucose ratios is short; pretty much just apples, watermelons, pears, and mangoes.
Some writers and online websites have taken to labeling fructose-induced asthma as “fructositis.” I am not fond of using this term, or at least applying it only to asthma, as excess free fructose consumption is now associated with a growing list of other inflammatory conditions aside from asthma. For example, a 2016 paper by the same authors as this current publication suggested that intake of excess fructose was associated with arthritis in US adults.12
High-fructose juices may be associated with asthma because of their high fructose-to-glucose ratio and underlying fructose malabsorption, which may contribute to enteral formation of pro-inflammatory advanced glycation end products (AGEs), which bind to receptors that are mediators of asthma. This sounds like we are speaking about gut biota here but at this point the research has not made that connection clear.
Advanced glycation end products are now considered the common denominator for predicting risk or prognosis for a list of chronic conditions including cardiovascular disease,11 neurodegenerative disease,12 liver disease,13 and diabetes.14
Up until quite recently the clinical focus was on preventing AGE formation during cooking.15 Attributing AGEs to enteral metabolism is a dramatic and recent shift in thinking. A decade ago the consensus was that these chemicals formed in food during cooking or food processing and thus all attention was directed to altering food preparation practices. These past assumptions may have been an oversimplification. While it is true that dietary intake of foods high in AGEs raises serum levels, a fact confirmed by a Dutch study published in June 2018,16 more attention is now focused on excess dietary fructose and the formation of AGEs in the intestine.17,18
Data on levels of these chemicals are usually obtained by measuring serum and urinary N-ε-carboxymethyl-lysine (CML); consumption of foods high in AGEs has not been as predictive of serum CML levels as once assumed. Apparently CML levels are more closely associated with fructose intake.19
Obviously, discouraging fructose intake may prove to be helpful in general, and perhaps helpful for asthma in particular.
There is a growing list of natural substances that inhibit formation of AGEs, suggested by at least in vitro research. How effective these substances will be at lowering AGEs in a clinical setting has yet to be determined.
The following are natural substances that may inhibit AGE formation:
- Phytates and, in particular, inositol hexaphosphate (commonly called IP6)20
- Curcumin and garlic21 or gallic acid22
- Coffee grounds23
- Chaga mushroom24
- White tea26
- Lipoic acid27
- Wild mint28
This is a rapidly evolving field of interest. For the moment probably the most important thing we can do for our patients is to help them recognize sources of fructose in their diet and to help them understand that fructose is no longer considered the “healthy sugar” it once was.