Is a fruit-rich diet bad for people with NAFLD? Original paper

In this 6-month randomized controlled trial, 72 participants (average age of 64, BMI between 18.5 and 29.9) with NAFLD (grade 2 or 3) were assigned to consume a fruit-rich diet (FRD) or a control diet. The participants in the FRD group were instructed to consume at least 4 servings of fruit per day, whereas the control group was instructed to consume no more than 2 servings of fruit per day. Dietary adherence was assessed monthly using three 24-hour recalls, and physical activity was assessed monthly using a questionnaire.

The outcomes assessed were liver fat (via ultrasonography), body weight, BMI, waist circumference, fasting blood glucose and insulin, homeostatic model assessment for insulin resistance (HOMA-IR), blood lipids, and liver enzymes.

The average fruit intake was 7 and 1.66 servings per day in the FRD and control groups, respectively. Body weight, BMI, waist circumference, glucose, insulin, HOMA-IR, triglycerides, low-density lipoprotein cholesterol, and liver enzymes increased in the FRD group, compared to the control group, whereas high-density lipoprotein cholesterol decreased in the FRD group. Also, the frequency of moderate and severe fatty liver was higher in the FRD group than the control group at the end of the study.

There was a lack of detail provided on the types of fruit consumed, which is notable because the calorie content in a serving of fruit significantly varies between fruits (e.g., banana vs. raspberry). In addition, close to half of daily fruit intake was composed of dried fruit in the FRD group, which tends to be calorically dense.

The researchers did not adjust for multiple comparisons, despite the inclusion of multiple outcomes, which increases the risk of false-positive results.

The most notable result from this study was the change in body weight between groups: body weight increased by 7 kg in the FRD group, whereas it decreased by 6.5 kg in the control group. As such, all this study indicates is that a hypocaloric diet reduces liver fat and improves cardiometabolic risk factors, whereas a hypercaloric diet has the opposite effects. These findings are already well known and have been consistently demonstrated in the literature.^[1]

While this study doesn’t provide any new information on the potential effects of a fruit-rich diet on liver health, it’s worth diving into the rest of the evidence on this topic to discern whether fruit intake should be limited to prevent the development and progression of NAFLD.

Hepatic de novo lipogenesis (DNL) is the process by which lipids are endogenously synthesized in the liver from carbohydrates. A couple of different lines of evidence suggest that DNL is an important contributor to the development of NAFLD,^[2] in that rates of DNL are substantially higher in people with NAFLD than in people with low liver fat,^[3] and when enzymes involved in DNL are inactivated in rodents, the typical increase in liver fat from consuming a high-fat, high-carbohydrate diet is attenuated.^[4]

Fructose has been highlighted as a nutrient concern because it acts as a substrate for DNL and stimulates DNL.^[4] In clinical trials, a high intake of fructose from fructose-sweetened beverages increased DNL compared to the same amount of energy from glucose-sweetened beverages or complex carbohydrates.^[5][6][7] Furthermore, fructose can indirectly increase DNL by blocking fatty acid oxidation in the liver.^[8]

The potentially unique effects of fructose on the liver stem from the way it’s metabolized. Compared to glucose, which is primarily metabolized in tissues outside of the liver, fructose is mostly metabolized in the liver. Additionally, compared to hepatic glucose metabolism, which is regulated by insulin and energy needs of the liver, hepatic fructose metabolism is unregulated.^[9] Thus, a high fructose intake can lead to excess substrate in the liver and increased DNL, facilitating liver fat accumulation.

Observational studies have reported that increased fructose intake is associated with an increased risk of NAFLD^[10][11] and an increased risk of fibrosis (i.e., scarring of the liver) in people with NAFLD.^[12][13]

Also, a high-fructose diet has been shown to induce fatty liver in rodents in the absence of weight gain,^[14][15] and there is some evidence to suggest that a high-fructose diet (about 25% of total energy intake) may increase liver fat independent of changes in body weight in humans.^[6][16][5] Even so, the totality of the available evidence suggests that the deleterious effects of fructose on liver health are really only a concern in the context of a hypercaloric diet with added fructose.^[17] Additionally, these effects have only been observed with a particular source of fructose: sugar-sweetened beverages.

A serving of fruit contains much less fructose than a serving of a sugar-sweetened beverage. Fruit also contains a lower amount of energy per unit and has a greater effect on satiety than sugar-sweetened beverages.^[18] Whereas the consumption of sugar-sweetened beverages is consistently associated with an increased risk of obesity and cardiometabolic disease, the consumption of fruit is inversely associated with these outcomes.^[19][18] Also, fruit contains a variety of polyphenols with beneficial health effects that may protect against NAFLD,^[20] as well as essential micronutrients.

In what appears to be the only other trial that assessed the effect of a fruit-rich diet on liver fat and cardiometabolic health, healthy participants consumed 9.58 grams of fresh fruit per kilogram of body weight per day (a nearly three-fold increase from baseline) for 8 weeks. At the end of the trial, there was a nonsignificant increase in body weight (+0.7 kilograms) and liver fat did not change, nor did blood lipids or fasting glucose.^[21]

Multiple lines of evidence suggest that a high-fructose diet can increase liver fat, primarily by increasing DNL, but there has yet to be a study in humans that demonstrated a clinically significant increase in liver fat without changes in body weight. The detrimental effects of fructose on liver health have been mostly observed in the context of a hypercaloric diet, and in studies that had participants consume a lot of fructose from sugar-sweetened beverages, not fresh fruit.

Because there were significant body weight changes in this study, it’s not possible to discern whether a fruit-rich diet in isolation has detrimental effects in people with NAFLD. If a fruit-rich diet significantly increases energy intake and thus increases body weight, then it can surely have detrimental effects, but most evidence suggests that a fruit-rich diet has a negative relationship with weight gain.^[18]

Further randomized controlled trials are needed to determine whether a eucaloric fruit-rich diet has adverse effects on liver health and cardiometabolic risk factors in people with NAFLD. As it stands, there’s a lack of evidence to support that limiting fruit intake helps to prevent the development or progression of NAFLD. Rather, consuming multiple servings of fresh fruit per day might have a protective effect.

The relationship between fructose intake and NAFLD

HFCS: high fructose corn syrup, DNL: de novo lipogenesis, ER stress: endoplasmic reticulum stress, VLDL: very low-density lipoprotein, Apo CIII: apolipoprotein C-III, TG: triglycerides, FA ox: fatty acids oxidation, LPS: lipopolysaccharide, BP: blood pressure, NAFLD: non-alcoholic fatty liver disease, MetS: metabolic syndrome.

Adapted from Corotani et al., 2022.^[22]