Effects of cafestol and kahweol from coffee grounds on serum lipids and serum liver enzymes in humans.

The diterpenes cafestol and kahweol are present in unfiltered coffee in oil droplets and floating fines. They elevate serum cholesterol and alanine aminotransferase (ALT). We measured fines in coffee brews, and examined diterpene availability from spent grounds in healthy volunteers. Turkish or Scandinavian boiled coffee contained 2-5 g fines/L and French press coffee contained 1.5 g fines/L. An intake of 8 g fine grounds/d for 3 wk increased cholesterol by 0.65 mmol/L (95% CI 0.41-0.89 mmol/L) and ALT by 18 U/L (95% CI 4-32 U/L) relative to control subjects (n = 7/group). In a crossover study (n = 15), mean serum cholesterol was 4.9 mmol/L after consumption of both fine and coarse grounds for 10 d (P = 0.43). Serum ALT activities were 29 U/L on fine and 21 U/L on coarse grounds (P = 0.02). Floating fines could contribute substantially to the hyperlipidemic and ALT-elevating effect of unfiltered coffee. Diterpene measurements in coffee brews should include the contribution of fines.

Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers.

BACKGROUND: An elevated plasma concentration of total homocysteine is considered to be a strong risk factor for cardiovascular disease. Heavy coffee drinking has been related to high homocysteine concentrations in epidemiologic studies and in one experiment in which healthy subjects drank unfiltered, boiled coffee. OBJECTIVE: Our goal was to determine whether daily consumption of paper-filtered coffee raises plasma concentrations of total homocysteine in healthy subjects. DESIGN: Twenty-six volunteers (18-53 y of age) consumed 1 L/d of paper-filtered coffee brewed with 70 g regular ground beans or no coffee for 4 wk each in a randomized, crossover design. RESULTS: The mean (+/-SD) plasma concentration of total homocysteine in fasting blood was 8.1 +/- 1.8 micromol/L after abstention from coffee and 9.6 +/- 2.9 micromol/L after 3-4 wk of coffee drinking, a difference of 1.5 micromol/L (95% CI: 0.9, 2.1 micromol/L) or 18% (P: < 0.001). Coffee increased homocysteine concentrations in 24 of 26 individuals. Circulating concentrations of vitamin B-6, vitamin B-12, and folate were unaffected. CONCLUSION: Drinking large quantities of paper-filtered coffee raises fasting plasma concentrations of total homocysteine in healthy individuals.

Separate effects of the coffee diterpenes cafestol and kahweol on serum lipids and liver aminotransferases.

The coffee diterpene cafestol occurs in both robusta and arabica beans. It is present in unfiltered coffee brews and raises serum concentrations of cholesterol, triacylglycerols, and alanine aminotransferase in humans. The effects are linear with the cafestol dose. Unfiltered coffee also contains the related compound kahweol, which occurs only in the major coffee strain arabica. The activity of kahweol is unknown. In a randomized, double-blind crossover study, we gave 10 healthy male volunteers either pure cafestol (61-64 mg/d) or a mixture of cafestol (60 mg/d) and kahweol (48-54 mg/d) for 28 d. Relative to baseline values, cafestol raised mean (+/-SEM) total serum cholesterol concentrations by 0.79 +/- 0.14 mmol/L (31 +/- 5 mg/dL), low-density-lipoprotein (LDL) cholesterol by 0.57 +/- 0.13 mmol/L (22 +/- 5 mg/dL), fasting triacy-glycerols by 0.65 +/- 0.12 mmol/L (58 +/- 11 mg/dL), and alanine aminotransferase by 18 +/- 2 U/L (all P < 0.01). Relative to cafestol alone, the mixture of cafestol plus kahweol increased total cholesterol by another 0.23 +/- 0.16 mmol/L (9 +/- 6 mg/dL) (P = 0.08), LDL cholesterol by 0.23 +/- 0.16 mmol/L (9 +/- 6 mg/dL) (P = 0.09), triacylglycerols by 0.09 +/- 0.10 mmol/L (8 +/- 9 mg/dL) (P = 0.20), and alanine aminotransferase by 35 +/- 11 U/L (P = 0.004). Thus, the effect of cafestol on serum lipid concentrations was much larger than the additional effect of kahweol, and the hyperlipidemic potential of unfiltered coffee mainly depends on its cafestol content. Both cafestol and kahweol raised alanine aminotransferase concentrations, and their hyperlipidemic effect thus seems not to be coupled with their effect on liver cells.

The cholesterol-raising diterpenes from coffee beans increase serum lipid transfer protein activity levels in humans.

Cafestol and kahweol-diterpenes present in unfiltered coffee-strongly raise serum VLDL and LDL cholesterol and slightly reduce HDL cholesterol in humans. The mechanism of action is unknown. We determined whether the coffee diterpenes may affect lipoprotein metabolism via effects on lipid transfer proteins and lecithin:cholesterol acyltransferase in a randomized, double-blind cross-over study with 10 healthy male volunteers. Either cafestol (61-64 mg/day) or a mixture of cafestol (60 mg/day) and kahweol (48-54 mg/day) was given for 28 days. Serum activity levels of cholesterylester transfer protein, phospholipid transfer protein and lecithin:cholesterol acyltransferase were measured using exogenous substrate assays. Relative to baseline values, cafestol raised the mean (+/- S.D.) activity of cholesterylester transfer protein by 18 +/- 12% and of phospholipid transfer protein by 21 +/- 14% (both P < 0.001). Relative to cafestol alone, kahweol had no significant additional effects Lecithin:cholesterol acyltransferase activity was reduced by 11 +/- 12% by cafestol plus kahweol (P = 0.02). It is concluded that the effects of coffee diterpenes on plasma lipoproteins may be connected with changes in serum activity levels of lipid transfer proteins.

Daily moderate alcohol consumption increases serum paraoxonase activity; a diet-controlled, randomised intervention study in middle-aged men.

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Part of this inverse association may be explained by its effects on HDL. Paraoxonase, an HDL-associated enzyme, has been suggested to protect against LDL oxidation. We examined the effects of moderate consumption of red wine, beer and spirits in comparison with mineral water on paraoxonase activity in serum. In this diet-controlled, randomised, cross-over study 11 healthy middle-aged men consumed each of the beverages with evening dinner for 3 weeks. At the end of each 3 week period, blood samples were collected pre- and postprandially and after an overnight fast. Fasting paraoxonase activity was higher after intake of wine (P<0. 001), beer (P<0.001), and spirits (P<0.001) than after water consumption (149.4+/-111.1, 152.6+/-113.1, 152.8+/-116.5 and 143. 1+/-107.9 U/l serum), but did not differ significantly between the 3 alcoholic beverages. Similar effects were observed pre- and postprandially. The increases in paraoxonase activity were strongly correlated with coincident increases in concentrations of HDL-C and apo A-I (r=0.60, P<0.05 and r=0.70, P<0.05). These data suggest that increased serum paraoxonase may be one of the biological mechanisms underlying the reduced coronary heart disease risk in moderate alcohol consumers

Consumption of unfiltered coffee brews in elderly Europeans. SENECA Investigators.

OBJECTIVE: To quantify the consumption of unfiltered coffee brews, which contain the cholesterol-raising diterpenes cafestol and kahweol, in elderly subjects. DESIGN: Interviews of randomly selected elderly in the 1993 SENECA Study on Nutrition and the Elderly in Europe. SETTING: Nine towns in eight European countries (Denmark, France, Italy, the Netherlands, Portugal, Switzerland, Poland, and Northern Ireland/United Kingdom). SUBJECTS: 962 relatively healthy elderly persons (460 men, 502 women) born between 1913 and 1918. MAIN OUTCOME MEASURE: Daily coffee consumption, classified by brewing technique. RESULTS: About 90 percent of the examinees were daily coffee users in Roskilde/Denmark (population means; men 530 ml/d, women 425 ml/d) and Culemborg/the Netherlands (men 513 ml/d, women 285 ml/d), against only 12% in Marki/Poland (population means; men 14 ml/d, women 36 ml/d) and 7% in Coimbra/Portugal (men 8 ml/d, women 0 ml/d). Drip-filtered and instant coffee, which are poor in diterpenes, were the prevalent types in most survey towns. Espresso and mocha coffee, which contain intermediate amounts of diterpenes, were consumed daily by 31% of the coffee drinkers in Switzerland and by all coffee drinkers in Italy, but intake was too low to substantially affect serum cholesterol levels. Consumption of brews that are rich in diterpenes, such as cafetiere, boiled, or Turkish/Greek coffee, was negligible in all survey towns. CONCLUSIONS: Coffee drinking is common among elderly people in some European countries, but intake of cafestol and kahweol with unfiltered coffee brews is 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.

The cholesterol-raising factor from coffee beans.

Coffee beans and some types of coffee brew-not the regular types of coffee prepared with a paper filter or with soluble coffee granules-contain the diterpenes cafestol and kahweol. Cafestol and kahweol raise the serum concentration of cholesterol and triglycerides in humans, and they also appear mildly to affect the integrity of liver cells. Both effects are transient after withdrawal of the diterpenes, and it is as yet unsure whether these effects are associated. Patients at increased risk of heart disease who drink large amounts of coffee should be advised to select brews low in diterpenes.

Comparison of effect of cafetière and filtered coffee on serum concentrations of liver aminotransferases and lipids: six month randomised controlled trial.

OBJECTIVE: To study the effects of prolonged intake of cafetière coffee, which is rich in the diterpenes cafestol and kahweol, on serum aminotransferase and lipid concentrations. DESIGN: Randomised parallel controlled trial. SUBJECTS: 46 healthy men and women aged 19 to 69. INTERVENTION: Consumption of five to six strong cups (0.9 litres) a day of either cafetière (22 subjects) or filtered coffee (24 subjects) for 24 weeks. MAIN OUTCOME MEASURES: Mean changes in serum aminotransferase and lipid concentrations. RESULTS: Cafetière coffee raised alanine aminotransferase concentration by up to 80% above baseline values relative to filtered coffee. After 24 weeks the rise was still 45% (9 U/l (95% confidence interval 3 to 15 U/l), P = 0.007). Alanine aminotransferase concentration exceeded the upper limit of normal in eight of the 22 subjects drinking cafetière coffee, being twice the upper limit of normal in three of them. Cafetière coffee raised low density lipoprotein cholesterol concentrations by 9-14%. After 24 weeks the rise was 0.26 mmol/l (0.04 to 0.47 mmol/l) (P = 0.03) relative to filtered coffee. Triglyceride concentrations initially rose by 26% with cafetière coffee but returned close to baseline values within six months. All increases were reversible after the intervention was stopped. CONCLUSIONS: Daily consumption of five to six cups of strong cafetière coffee affects the integrity of liver cells as suggested by small increases in serum alanine aminotransferase concentration. The effect does not subside with prolonged intake. High intakes of coffee brews rich in cafestol and kahweol may thus be responsible for unexplained increases in this enzyme activity in apparently healthy subjects. Cafetière coffee also raises low density lipoprotein cholesterol concentration and thus the risk of coronary heart disease.

[Dietary trans-fatty acids: a risk factor for coronary disease]. / Transvetzuren in de voeding: risico op coronaire hartziekten.

Unsaturated fatty acids with their double bond in trans configuration raise serum low-density lipoprotein (LDL) cholesterol and lipoprotein(a) levels, and lower high-density lipoprotein (HDL) cholesterol in humans when substituted for cis unsaturated fatty acids in the diet. These effects should increase the risk of coronary heart disease, which is confirmed by epidemiological studies. Trans fatty acids are formed from cis unsaturated fatty acids during hydrogenation of vegetable oils in food industries. Until recently, major dietary sources of trans fatty acids in the Netherlands were frying fats, shortenings, and margarines, which in the past contained up to 50% of trans fatty acids. Nowadays, most shortenings and margarines sold in the Netherlands have a low trans fatty acid content due to manufacturing changes in the recent past. However, frying fats used in fast-food outlets still contain over 30% of trans fatty acids. French fries sold in these outlets provide 7-8 g of trans fatty acids per portion. Producers of frying fats for fast-food outlets therefore should also reduce the trans fatty acid content of their products as much as possible.

The cholesterol-raising factor from coffee beans.

Some coffee brewing techniques raise the serum concentration of total and low-density-lipoprotein cholesterol in humans, whereas others do not. The responsible factors are the diterpene lipids cafestol and kahweol, which make up about 1% (wt:wt) of coffee beans. Diterpenes are extracted by hot water but are retained by a paper filter. This explains why filtered coffee does not affect cholesterol, whereas Scandinavian "boiled," cafetiere, and Turkish coffees do. We describe the identification of the cholesterol-raising factors, their effects on blood levels of lipids and liver function enzymes, and their impact on public health, based on papers published up to December 1996.

Differences between men and women in the response of serum cholesterol to dietary changes.

BACKGROUND: Hypercholesterolaemia is initially treated by diet. However, most studies of diet and cholesterol response have been carried out in men, and it is not known whether women react to diet to the same extent as men do. We therefore studied sex differences in the response of serum cholesterol and lipoproteins to diet. MATERIALS AND METHODS: We measured the responses of serum cholesterol to a decrease in dietary saturated fat in seven trials involving 126 men and 147 women, to a decrease in dietary trans fat in two trials (48 men and 57 women) and to a decrease in dietary cholesterol in eight trials (74 men and 70 women). We also measured responses to the coffee diterpene cafestol, which occurs in unfiltered coffee, in nine trials (72 men and 61 women). All subjects were lean and healthy. RESULTS: The response of total cholesterol (+/- standard deviation) to a decrease in the intake of saturated fat was greater in men (-0.62 +/- 0.39 mmol L-1) than in women (-0.48 +/- 0.39 mmol L-1; 95% confidence interval, 0.04-0.23 mmol L-1). The response of total cholesterol to a decrease in the intake of cafestol was also larger in men (-1.01 +/- 0.49 mmol L-1) than in women (-0.80 +/- 0.49 mmol L-1; 95% confidence interval, 0. 04-0.39 mmol L-1). Responses to trans fat and to dietary cholesterol did not differ between men and women. CONCLUSION: Men have larger responses of total and low-density lipoprotein cholesterol to saturated fat and cafestol than women do.

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.

Consumption of French-press coffee raises cholesteryl ester transfer protein activity levels before LDL cholesterol in normolipidaemic subjects.

OBJECTIVES: To determine the long-term effects of unfiltered coffee consumption on the activity levels of cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP) and lecithin:cholesterol acyltransferase (LCAT) and to assess a possible role of CETP activity levels in the rise in serum LDL cholesterol. SUBJECTS AND DESIGN: Forty-six healthy normolipidaemic subjects consumed 0.9 L of either French-press or filtered coffee for 24 weeks. Fasting blood samples were obtained after 0, 2, 12 and 24 weeks of intervention and after and 12 weeks of follow-up. MAIN OUTCOME MEASURES: Serum activity levels of CETP, PLTP and LCAT. RESULTS: Relative to baseline, French-press coffee significantly increased average CETP activity by 12% after 2 weeks, by 18% after 12 weeks, and by 9% after 24 weeks. PLTP activity was significantly increased by 10% after 12 and 24 weeks. LCAT activity was significantly decreased by 6% after 12 weeks and by 7% after 24 weeks. The increase in CETP clearly preceded the increase in LDL cholesterol, but not the increase in total triglycerides. However, consumption of French-press coffee caused a persistent rise in CETP activity, whereas the rise in serum triglycerides was transient. CONCLUSIONS: Consumption of cafestol and kahweol cause a long-term increase in CETP as well as PLTP activity; the increase in CETP activity may contribute to the rise in LDL cholesterol.