The hypercholesterolemic effect of cafestol in coffee oil in gerbils and rats.

Coffee beans contain the diterpene cafestol, which raises plasma cholesterol concentrations in humans. Daily consumption of 2 g coffee oil, which provides approximately 60 mg cafestol (equivalent to 5.7 mg cafestol/MJ), increases plasma cholesterol concentrations by 28%. We studied the effect of cafestol in coffee oil on gerbils and rats to determine whether the pathways that lead to cafestol-induced hypercholesterolemia in humans are also present in other species. We fed coffee oil from the same batch used in humans to female gerbils and rats. Gerbils were fed a semipurified diet containing 0.5% or 5% (w/w) coffee oil (equivalent to 8.7 and 86.8 mg cafestol/MJ, respectively) in the presence or absence of 0.05% (w/w) cholesterol for a period of 10 weeks. When compared with the gerbils fed no coffee oil, the addition of 0.5% coffee oil to the diets did not affect plasma cholesterol. Plasma cholesterol was significantly higher only when 5% coffee oil was fed, both in the absence (1.01 mmol/L, 33% higher) and presence (1.87 mmol/L, 70% higher) of dietary cholesterol. Liver weight was also significantly higher when 5% coffee oil was fed. Rats were also fed diets containing 0.5% or 5% coffee oil (equivalent to 8.7 and 86.8 mg cafestol/MJ) with and without 0.05% cholesterol for 8 weeks. Feeding 0.5% coffee oil compared with no coffee oil resulted in significantly higher plasma cholesterol levels throughout the study both in the absence (0.46 mmol/L, 27% higher) and presence (0.28 mmol/L, 15% higher) of dietary cholesterol. Diets containing 5% coffee oil appeared to be toxic. Thus, coffee oil diterpenes can result in higher plasma cholesterol in gerbils and rats. The failure to observe these effects in previous studies may be due to doses that were too low.

Diterpenes from coffee beans decrease serum levels of lipoprotein(a) in humans: results from four randomised controlled trials.

OBJECTIVE: Unfiltered coffee raises serum LDL cholesterol in humans, owing to the presence of the diterpenes cafestol and kahweol. Norwegians with a chronic high intake of unfiltered coffee also has elevated serum levels of lipoprotein(a), an LDL-like particle which is insensitive toward dietary interventions. We now experimentally studied the influence of coffee diterpenes on lipoprotein(a) levels. DESIGN: Four randomised controlled trials. SUBJECTS: Healthy, normolipidemic volunteers. INTERVENTIONS: Coffee, coffee oil, and pure diterpenes for 4-24 weeks. MAIN OUTCOME MEASURES: The circulating level of lipoprotein(a). RESULTS: In 22 subjects drinking five to six strong cups of cafetiere coffee per day, the median fall in lipoprotein(a) was 1.5 mg/dL after two months (P = 0.03), and 0.5 mg/dL after half a year (P > 0.05), relative to 24 filter coffee drinkers. Coffee oil doses equivalent to 10-20 cups of unfiltered coffee reduced lipoprotein(a) levels by up to 5.5 mg/dL (P < 0.05) in two separate trials (n = 12-16 per group). A purified mixture of cafestol and kahweol, as well as cafestol alone, were also effective in reducing Lp(a) levels (n = 10). Averaged over the four trials, each 10 mg/d of cafestol (plus kahweol)--the amount present in two to three cups of cafetiere coffee--decreased Lp(a) levels by 0.5 mg/dL or 4% from baseline values after four weeks (n = 63). CONCLUSIONS: Coffee diterpenes are among the few dietary exceptions shown to influence serum lipoprotein(a) levels. However, the Lp(a)-reducing potency of coffee diterpenes may subside in the long run, and their adverse side effects preclude their use as lipoprotein(a)-reducing agents.

Chronic consumers of boiled coffee have elevated serum levels of lipoprotein(a).

OBJECTIVES: Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boiled coffee and serum levels of lipoprotein(a). DESIGN, SETTING AND SUBJECTS: Healthy Norwegians 40-42 years of age, who habitually consumed five or more cups of boiled coffee per day (n = 150) were compared with matched filter coffee consumers (n = 159) in a cross-sectional study, as part of the Norwegian National Health Screening in 1992. RESULTS: The median lipoprotein(a) level was 13.0 mg dL-1 (10th and 90th percentile: 2.5 and 75.0 mg dL-1, respectively) on boiled and 7.9 mg dL-1 (10th and 90th percentile: 1.9 and 62.5 mg dL-1, respectively) on filter coffee (P = 0.048). Means +/- SE were 25.8 +/- 2.4 mg dL-1 and 19.6 +/- 2.0 mg dL-1, respectively (P = 0.04). Although not statistically significant, subjects consuming nine or more cups of coffee per day had higher lipoprotein(a) levels than those drinking five to eight cups per day in both coffee groups. CONCLUSION: Chronic consumers of unfiltered, boiled coffee have higher serum levels of lipoprotein(a) than filter coffee drinkers.

Boiled coffee fails to raise serum cholesterol in hamsters and rats.

Boiled coffee contains the lipid compounds cafestol and kahweol, which raise cholesterol strongly in man. These lipids are retained by paper filters. In a search for an animal model for the effect of coffee lipids on serum cholesterol concentrations, we fed hamsters (Mesocricetus auratus) and rats on mash diets consisting of a purified base diet and either boiled water, unfiltered boiled coffee or filtered boiled coffee. After a feeding period of 8 weeks there was no statistically significant effect of unfiltered boiled coffee on serum total cholesterol and triacylglycerol concentrations in either the hamsters or the rats. The level of serum cholesterol did respond predictably to the addition of cholesterol and/or saturated fatty acids to the diet. The lack of effect of unfiltered boiled coffee in the hamsters and the rats, when compared with the previously reported activity in humans, could not be explained by dosage, duration of treatment, mode of administration or by insufficient statistical power. It is concluded that hamsters and rats are insensitive to unfiltered boiled coffee and thus are unsuitable models for investigating its hypercholesterolaemic effect.

Coffee oil consumption does not affect serum cholesterol in rhesus and cebus monkeys.

Oil from coffee beans contains the diterpenes cafestol and kahweol, which greatly elevate cholesterol in humans. Consumption of 0.03 g coffee oil (0.86 mg cafestol and 1.04 mg kahweol)/kg body wt raised serum cholesterol by 1.27 mmol/L in volunteers. We fed coffee oil from this same batch to cebus and rhesus monkeys. Two groups of eight cebus monkeys were fed a purified diet containing 0.5% coffee oil or placebo oil (sunflower plus palm oil, 3:2, wt/wt) for 2 x seven and a half weeks in a crossover design. The daily intake of the coffee oil was 0.18 g (5.13 mg cafestol and 6.21 mg kahweol)/kg body wt, or sixfold that in the human study. Coffee oil did not affect plasma cholesterol or triglyceride concentrations compared with the placebo oil. Two groups of three rhesus monkeys were fed a commercial diet containing either 0.5% coffee oil or 0.5% placebo oil for 2 x 6 wk in a crossover design. The daily intake of coffee oil was 0.20 g (5.70 mg cafestol and 6.90 mg kahweol)/kg body wt. Again, there was no effect of coffee oil on plasma cholesterol or triglyceride concentrations. Contrary to the findings in human studies, coffee oil had no impact on plasma alanine aminotransferase activity in nonhuman primates. The cholesterol-raising effect of diterpenes from coffee oil, present in boiled coffee, seems to be specific for human primates.

Diterpene composition of oils from Arabica and Robusta coffee beans and their effects on serum lipids in man.

OBJECTIVES: The cholesterol-raising effect of boiled coffee is caused by diterpenes from coffee oil. In order to identify the diterpene responsible, we analysed the diterpene composition of oils from Arabica (Coffea arabica) and Robusta (Coffea canephora robusta) beans and their effects on serum lipids and thyroid function. DESIGN, SUBJECTS, AND INTERVENTION: During the first 3-week period of a randomized, cross-over trial, 11 healthy, normolipaemic volunteers received per day either 2 g of coffee oil (n = 5) or placebo oil (n = 6). After a 2-week wash-out, the reverse treatments were applied for another 3 weeks. Six subjects received Arabica oil, supplying 72 mg day-1 cafestol and 53 mg day-1 kahweol, and five received Robusta oil, which provided 40 mg of cafestol, 19 mg of 16-O-methyl-cafestol, and 2 mg of kahweol per day. Background diets were constant. RESULTS: The average serum cholesterol levels rose by 0.65 mmol L-1 (13%) on Arabica oil (P < 0.025; 95% CI, 0.21-1.09 mmol L-1) and by 0.53 mmol L-1 (13%) on Robusta oil (NS; 95% CI -0.36-1.42 mmol L-1). The triglycerides levels rose by 0.54 mmol L-1 (71%) on Arabica (P < 0.005; 95% CI, 0.22-0.76 mmol L-1) and 0.49 mmol L-1 (61%) on Robusta oil (P < 0.005; 95% CI, 0.30-0.68 mmol L-1). None of the effects on serum lipids or lipoprotein cholesterol levels was significantly different between Arabica and Robusta oil. Concentrations of serum total and free thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were largely unaffected. CONCLUSIONS: Both Arabica and Robusta oil elevated serum lipid levels; therefore, cafestol must be involved and kahweol cannot be the sole cholesterol-raising diterpene. The mode of action of coffee diterpenes does not involve induction of hypothyroidism.

Identity of the cholesterol-raising factor from boiled coffee and its effects on liver function enzymes.

Boiled coffee contains an unidentified lipid that raises serum cholesterol. We studied the effects of the ingestion of coffee oil fractions of increasing purity in volunteers in order to identify the cholesterol-raising factor. In 15 volunteers who ingested 0.75 g/d of a non-triglyceride-fraction from coffee oil for 4 weeks, mean cholesterol increased by 48 mg/dl (1.2 mmol/l) relative to placebo. In contrast, a coffee oil stripped of the non-triglyceride lipids cafestol and kahweol had no effect. In three volunteers, purified cafestol (73 mg/d) plus kahweol (58 mg/d) increased cholesterol by 66 mg/dl (1.7 mmol/l) after 6 weeks. Oil from Robusta beans, which contains cafestol but negligible kahweol, also raised serum cholesterol. These findings show that cafestol is at least partly responsible for the cholesterol-raising effect of boiled coffee. Coffee oils and brews containing cafestol consistently increased serum triglycerides and alanine amino-transferase, and depressed serum creatinine and gamma-glutamyl-transferase (GGT). After withdrawal GGT activity rose above baseline. Norwegians who habitually consumed 5-9 cups of boiled coffee per day had higher serum cholesterol levels and lower GGT but no higher alanine aminotransferase activity than controls. Thus, serum cholesterol is raised by cafestol and possibly also kahweol, both natural components of coffee beans. The mechanism of action is unknown but is accompanied by alterations in liver function enzymes.