By Dr. Geoffrey Modest
A recent study found that fructose consumption and serum uric acid were independently associated with non-alcoholic steatohepatitis (NASH) in obese kids with non-alcoholic fatty liver disease (NAFLD), (see doi.org/10.1016/j.jhep.2016.12.025).
- 271 obese children (by BMI) with NAFLD were studied
- NASH was diagnosed by biopsy, with a NAFLD score of at least 5, and by the fatty liver inhibition of progression (FLIP) algorithm (another algorithm for the diagnosis of NASH)
- Fructose intake was determined by a food frequency questionnaire
- Hyperuricemia was defined as a serum uric acid level >5.9 mg/dl
- NASH occurred in 37.6% of the children
- Mean age 11.5, 38% female, BMI 27, waist circumference 87cm, AST 48/ALT 62, uric acid 5.8, LDL 100/HDL 45, BP 112/68, TNF-a Of note, there were significant differences between those with NASH and those without, but only for: waist circumference, AST/ALT, total cholesterol (but not LDL, HDL alone), triglycerides, fructose consumption, and TNF- a
- Hyperuricemia was found in 47% of the kids with NASH, vs 29.7% without NASH (p=0.003)
- Adjusting for multiple measured confounders:
- Uric acid level was associated with NASH, OR 2.49 (1.87-2.83), p=0.004
- Fructose consumption was associated with NASH, OR 1.61 (1.25-2.85), p=0.001
- These associations with NASH were independent of each other
- Though, fructose consumption was still independently associated with hyperuricemia, OR 2.02 (1.66-2.78), p=0.01
- These data on NASH were confirmed by using the FLIP algorithm
- As noted in prior blogs, there seems to be a pretty consistent relationship between fructose consumption and uric acid levels, as was shown in this study. And there are data suggesting that dietary fructose can be part of the pathogenesis of NAFLD (induction of de novo lipogenesis, inflammation, insulin resistance). Studies in adults have found that hyperuricemia is associated with insulin resistance, type II diabetes and metabolic syndrome.
- There are many dietary sources of fructose. The major ones for most people are table sugar (sucrose, a disaccharide of glucose and fructose) and high fructose corn syrup (in a surprising number of foods, as a very cheap and potent sweetener). Perhaps the “low-hanging fruit” here is sodas, consumed by very large numbers of people (https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a2.htm#Tab2 , finding that on average 26.3% of US adults consume at least one sugar-sweetened beverage daily, up to 41.4% in Mississippi, the highest of states, and that soda by itself was consumed by 24.5% of those 18-34 yo, and 47.4% in Mississippi). And a NHANES study (Welsh JA. JAMA 2010; 303(15): 1490) found that on average, 15.8% of calories came from added sugars, and that >25% of the patients got >25% of their total energy from added sugar. My experience is that it is easier to help people stop sodas and juices, substituting water, than other dietary interventions.
- I am not sure why we focus so exclusively on BMI, since the data are pretty consistent over the decades that abdominal obesity is really the bad actor, more metabolically active and associated with inflammatory markers, diabetes/insulin resistance/metabolic syndrome and is independently associated with cardiovascular risk (BMI is not: its association is mediated by its association with other risk factors, such as blood pressure, lipids). Waist circumference is a much better, though not perfect, marker of visceral obesity than BMI. That being said, there is a pretty strong relationship (but not always) between BMI and waist circumference, especially in those with BMI >35. The most reasonable recommendations I have seen is to measure the waist circumference regularly, especially if the BMI is between 25-35. Although practically we should reinforce lifestyle changes in all patients with high BMI, independent of waist circumference, I think the patient should understand that for those with a high waist circumference, their cardiometabolic risk is even higher. See http://blogs.bmj.com/bmjebmspotlight/2015/12/02/primary-care-corner-with-geoffrey-modest-md-central-obesity/ for the fuller argument
So, this study does add some important information: it confirms that both uric acid levels and fructose are associated with NASH in kids that they are associated with each other, but that they are also independent predictors (and there are several studies which show that decreasing fructose consumption, as in sodas, is associated with decreased uric acid levels. See blogs below). So, bottom line is that fructose consumption is bad and should be decreased, even if the uric acid level is just fine.
See http://blogs.bmj.com/bmjebmspotlight/2015/12/11/primary-care-corner-with-geoffrey-modest-md-fructose-restriction-and-cardiometabolic-and-weight-improvement/ for prior blog of fructose consumption in kids and cardiometabloic and weight improvements
http://blogs.bmj.com/bmjebmspotlight/2016/09/13/primary-care-corner-with-geoffrey-modest-md-non-alcoholic-fatty-liver-disease-3/ is one of 3 articles on NAFLD, highlighting an important role of fructose
http://blogs.bmj.com/bmjebmspotlight/2016/03/18/primary-care-corner-with-geoffrey-modest-md-microbiome-changes-and-severity-of-nafld/ more on the microbiome and hepatic changes with fructose