Robusta oil caused a rise of ALAT levels of more than 2.5 times the upper limit of normal in three out of eighteen subjects (17%). In our previous study with Arabica oil we observed ALAT levels of more than 2.5 times the upper limit of normal in eight out of 50 subjects (16%) in the first period and in five of 40 subjects (13%) not in the first, but only in a second treatment period [11]. Therefore we conclude that the effect of Robusta oil on liver enzyme levels is similar to that of Arabica oil. Levels of ASAT were less affected by coffee oil than ALAT levels. ALAT is predominantly present in the cytosol of hepatocytes, whereas ASAT is predominantly present in the mitochondria. This could mean that the outer membranes of hepatocytes have become leaky but that the cells are still largely intact. When hepatocytes sustain more severe damage, the serum levels of ASAT would exceed those of ALAT [6–8]. ALAT levels were also elevated in subjects after daily consumption of unfiltered coffee for six months [12], but were not elevated in life-long consumers [1, 13]. This suggests that the effect of unfiltered coffee on ALAT levels is transient when consumed over long periods of time and that possibly an adaptation mechanism is present.
Another marker of liver damage, γ-glutamyltranspeptidase (γGT), has been shown to decrease during consumption of boiled coffee. After withdrawal of treatment with coffee lipids or coffee oil an rebound increase above baseline values in serum levels of γGT is observed [1, 3, 14, 15]. In the present study we observed a 14% decrease in serum activities of γGT during treatment and an increase of 17% compared to baseline eight weeks after termination. These effects are not statistically significant in the present study. This is due to the limited number of subjects and the short duration of the coffee oil treatment. We also observed a 7% decrease in serum activities of alkaline phosphatase compared to baseline four weeks after termination. A tendency of alkaline phosphatase to be decreased during coffee lipid treatment was observed in previous studies [1, 3]. Bilirubin levels were 38% increased during the follow-up measurement after four weeks compared to baseline. We observed no effect of Robusta oil treatment on amylase, a marker for pancreatitis, or lactate dehydrogenase, which is used for diagnosis of heart, muscle, and liver diseases. Increases of γGT and bilirubin after stopping treatment with coffee oil could indicate cholestasis. Cholestasis is functionally defined as a disruption in secretion of bile acids from the liver. Disrupted secretion causes elevated levels of bile acids in the liver, which causes damage to the hepatocytes. However, in cholestatic disease alkaline phosphatase is strongly increased, which is not the case with coffee oil treatment.
In Scandinavia, where large amounts of unfiltered coffee were commonly consumed, risk of coronary heart disease is high and was associated with consumption of unfiltered coffee but mortality rates of liver cirrhosis have been typically low [16]. Therefore, it is unlikely that consumption of unfiltered coffee produces severe damage to the liver. However, it is possible that unfiltered coffee can cause sub-clinical hepatic injury in some individuals. At present we have no evidence that the changes in liver enzyme levels induced by coffee oil or unfiltered coffee are of clinical relevance. Because we have no liver biopsies from subjects we are not able to demonstrate possible liver damage in vivo. No results from animal studies showing the effect of coffee oil on the liver have been published.
Interestingly, cafestol and kahweol have been shown to upregulate detoxification pathways in the liver of rat and mice and human cultured cells [17–21]. This effect on detoxification is hypothesized to explain the observed inverse association between coffee consumption and certain cancer types [20, 22–24]. Possibly, cafestol upregulates these pathways due to its toxicity and as a "side effect" enhances detoxification of carcinogenic compounds.
After 16 days of Robusta oil treatment serum cholesterol levels were elevated but this effect was not statistically significant at the P < 0.05 level according to the conventional frequentist analysis. This was expected from previous studies: the full effect on serum cholesterol is only observed after 4–6 weeks of coffee oil consumption. After four weeks daily consumption of 62 mg of cafestol results in a rise in serum cholesterol of 0.8 mmol/l. The Bayesian analysis, however, indicates that the present study in fact reinforces the existing evidence that coffee oil raises serum cholesterol, independent of how strong one judges this prior evidence to be (Table 3). We also found that triglycerides were elevated after 16 days of treatment, which was also expected from previous studies [1–4].
On the basis of our results it is not likely that it is kahweol, which is mainly responsible for the effect of coffee oil on liver enzyme levels, as has been suggested in two previous studies [3, 9]. In most subjects coffee oil caused elevation of liver enzyme levels. However, this elevation was more extreme in a small number of subjects. Figure 2 shows ALAT levels and figure 3 shows ASAT levels of subjects at baseline and after 16 days of coffee oil consumption. Although no parallel placebo group was present in this study it is unlikely that such large responses of liver enzymes would be observed with placebo oil. This is supported by previous studies with coffee and placebo oil [1, 9, 25]. We found no correlation between the response of liver enzymes to coffee oil and baseline liver enzyme activities, serum lipid response, or alcohol. Moreover, a previous study showed that the liver enzyme response is not consistent within subjects [11]. In this study we also found no correlation between alcohol intake and liver enzyme response. Although we cannot rule out the possibility that alcohol affected the liver enzyme response during the study it does not seem likely that alcohol intake could fully explain the observed increases in ALAT and ASAT. Furthermore, γGT is decreased rather than increased during consumption of coffee oil, whereas alcohol causes increases in γGT levels.
Together with the observation that most subjects do not show such a large increase in liver enzyme levels during coffee oil treatment, this suggests that an unknown environmental factor enhances the response of liver enzymes to coffee oil in a number of subjects. We conclude that increased ALAT or ASAT activities in patients may be caused by a switch from filtered to unfiltered coffee. If raised activities of ALAT and ASAT are caused by a change in coffee consumption, the ratio ASAT/ALAT will be smaller then 1 and other markers of liver damage such as γGT and alkaline phophatase will be typically within normal limits. When otherwise unexplained elevation of ALAT and ASAT activities are observed it would be advisable to ask a patient if he/she consumes large amounts of unfiltered coffee such as French press coffee.