Effects of a high monounsaturated fat, tomato-rich diet on serum levels of lycopene

Abstract

Objective: To compare the effect of a modified fat, monounsaturated-fat-enriched diet and a high-carbohydrate low-fat diet with high lycopene content on the serum concentration of lycopene and other carotenoids.

Design: A randomised crossover dietary intervention study.

Setting:Melbourne, Australia — Healthy free-living men.

Subjects: A total of 13 healthy males between the age of 20 and 70 y, recruited via advertisements in newspapers and university newsletter.

Intervention: A randomised dietary intervention with two diets of 14 days each. The two diets were — (1) high-fat monounsaturated-fat-enriched (MUFA) and (2) high-carbohydrate low-fat (HCLF). Both the diets contained the same basic foods and a controlled carotenoid content high in lycopene.

Results: A significant increase in serum total lycopene occurred, by 126% on the MUFA diet (P<0.001) and 108% on the HCLF diet (P=0.001). A reduction in serum cryptoxanthin (27% on MUFA diet and 25% on HCLF) and alpha-carotene (43% on the MUFA diet and 25% on the HCLF diet) was observed. No change was observed for the other carotenoids. Comparing the end of the two diets, no statistically significant difference was observed for lycopene or the other carotenoids.

Conclusion: In all, 15% of energy from fat or 38% of energy from fat (predominantly monounsaturated fat) in the diet does not have a significant differential effect on serum lycopene.

Sponsorship: The study was partially funded by the Grains Research Development Corporation, Canberra and Meadow Lea Foods Ltd, Mascot, Australia. HJ Heinz, Melbourne, Australia provided the tomato products and some funds for their carotenoid analysis.

Introduction

The Seven Countries Study indicated that the Greeks, with a high intake of monounsaturated fat, plant foods, grains, cereals and low intake of meat and dairy, and also the Japanese, with a low-fat, high-carbohydrate intake, have a lower incidence of heart disease compared to the US populations with a high intake of saturated fat, meat and dairy products (Kromhout, 1989). Meta-analyses suggest that the replacement of saturated fat with other energy sources may reduce the risk of heart disease (Mensink & Katan, 1992; Clarke, 1997; Parks & Hellerstein, 2000), but it remains debatable which energy source is the optimal replacement. Some researchers advocate replacement with monounsaturated fats (Katan et al, 1997; de Lorgeril et al, 1999), while others suggest reducing the total fat intake and increasing the energy from carbohydrates (Watts et al, 1992; Haskell et al, 1994; Ornish et al, 1998). Smaller intervention studies have shown that both high-monounsaturated fat diets and high-carbohydrate low-fat diets decrease serum total cholesterol and low-density lipoprotein (LDL) cholesterol levels. However, the effects on high-density lipoprotein (HDL) cholesterol and triglycerides have been inconclusive (Garg et al, 1988; Grundy et al, 1988; Ashton et al, 2001).

In the 1960s Mediterraneans consumed more fruits and vegetables than US populations (Kromhout, 1989). This observation led researchers to look for the components of fruits and vegetables that might be inversely related to coronary heart disease (CHD). Recent interest has focussed on the effects of carotenoids in the diet and/or serum on certain degenerative diseases. Epidemiological data suggest that high serum levels of carotenoids and/or high dietary intake of carotenoids contribute in reducing the risk of certain chronic diseases. It has been suggested that serum levels of lycopene (Klipstein Grobusch et al, 2000; Rissanen et al, 2001) and beta-carotene (Street et al, 1994; D'Odorico et al, 2000) are inversely related to the risk of cardiovascular disease. In addition, individual dietary carotenoids are thought to account for specific protective effects. It has been suggested, for example, that tomatoes and tomato products rich in lycopene are inversely related to the risk of prostate cancer (Giovannucci et al, 1995; Norrish et al, 2000). Carotenoids like lutein and zeaxanthin have been found to be associated with a lower risk of cataracts (Jacques & Chylack, 1991; Chasan-Taber et al, 1999) and macular degeneration (Seddon et al, 1994). A dietary intake of alpha-carotene is inversely related to the risk of lung cancer (Michaud et al, 2000). Bladder cancer appears to be inversely related to the intake of beta-cryptoxanthin (Zeegers et al, 2001). Some research suggests an inverse relation between dietary beta-carotene and lung cancer (Le Marchand et al, 1993), but long-term intervention trials have shown no effect (Hennekens et al, 1996) or a detrimental effect of supplemental beta-carotene on the incidence of lung cancer in smokers (ATBC, 1994; Omenn et al, 1996).

Serum carotenoid levels reflect the immediate carotenoid intake (Rock et al, 1992; Yeum et al, 1996; Lee et al, 2000). Even so, pathophysiological factors such as poor iron, zinc or protein status, malabsorption diseases and liver or kidney disease may result in reduced carotenoid absorption (Williams et al, 1998). Similarly, drugs that affect cholesterol absorption have been suggested to inhibit carotenoid absorption (Elinder et al, 1995). Gender, season, smoking and alcohol intake also influence serum carotenoid concentrations (Olmedilla et al, 1994; Forman et al, 1995; Olmedilla Alonso et al, 1997; Wei et al, 2001), and some carotenoids also compete for absorption and/or interact with each other to affect their bioavailabilty (Kostic et al, 1995; Johnson et al, 1997).

Lycopene, an acyclic carotenoid mainly found in tomatoes, has been suggested to have the greatest antioxidant capacity of the carotenoids found in fruits and vegetables, followed by beta-carotene, cryptoxanthin and lutein/zeaxanthin (Di Mascio et al, 1989; Miller et al, 1996; Mortensen et al, 1997). However, this may differ depending upon the assay and the circumstances involved for determining the antioxidant capacity (Paiva & Russell, 1999). Carotenoids, including lycopene, are fat-soluble compounds and their absorption involves solubilisation in the bile salts and incorporation in micelles. As the presence of dietary fat is important for micelle formation in the small intestine, the absorption of carotenoids from the diet into the body may also depend on the amount of fat ingested. The intake of carotenoid-rich foods cooked with oil increases the serum carotenoid bioavailability (Stahl & Sies, 1992). The effects of different amounts of oil in the diet on the serum concentration of beta-carotene (Jayarajan et al, 1980; Dimitrov et al, 1988; Jalal et al, 1998) and lutein (Roodenburg et al, 2000) have been studied.

The present study was conducted to compare the effects of two lycopene-enriched, other carotenoid-controlled diets, one a monounsaturated-fat-enriched (MUFA) diet and the other a high-carbohydrate low-fat (HCLF) diet, on the serum concentration of lycopene. Other carotenoids were also measured to observe any major effects, and serum lipids and lipoproteins were used to determine any differential effects on these CHD risk factors.

Methods

A total of 13 healthy men aged 20–70 y, recruited via advertisements in newspapers and university newsletters, volunteered for this randomised crossover dietary study. Results from previous studies indicated that this sample size would give 80% power to detect a 20% difference in serum lycopene with an alpha of 0.05. Only male subjects were recruited because gender differences may affect the serum carotenoid levels, especially beta-carotene and alpha-carotene (Olmedilla et al, 1994). Subjects were non-smokers, had no history of cardiovascular, hepatic or renal disease and had not adhered to any special diets at least 4 weeks prior to participating in the study. The Deakin University Ethics Committee, Melbourne, Australia, approved the study and all volunteers gave written informed consent. Weight measurements for each subject were taken at the start and at the end of each dietary period. Height was measured at the start of the first dietary period.

Dietary design and analysis

Subjects completed a 4 day weighed food record diary, encompassing three consecutive weekdays and one weekend day. Subjects were provided with food weighing scales (Bosco, model 312 AND Medical Products, Kensington, Australia) and detailed verbal and written instructions on how to record the amount of food and drink consumed during the 4 days. The records were analysed using Food Works version 2.01 using NUTTAB 95 (Xyris Software, Brisbane, Australia). When foods were not present in the database (eg health foods), the nutrient compositions supplied by the manufacturer were manually added to the database, or foods with the closest composition were selected. The energy intake on the usual diets was used to design the diets for the intervention periods.

Diets

Figure 1 presents the study protocol. To avoid any acute peaks in the serum carotenoid concentrations, which may occur because of a high carotenoid intake 10–12 h before blood samples are taken (Porrini et al, 1998), subjects were asked to eat a low-carotenoid diet (LCD) 2 days before starting the dietary intervention periods. A list of acceptable and nonacceptable foods was provided for this LCD. Using a computer-generated randomisation number sheet, the volunteers were assigned to receive either the MUFA diet or the HCLF diet. After a ‘washout’ period of 6 weeks on their usual diet, the subjects ate the LCD diet for 2 days and then started the second dietary period of either HCLF diet or MUFA diet. Each diet was of 14 days duration. A set menu plan was designed for each person for the two dietary periods (MUFA and HCLF), which contained the same basic foods but different amounts of fat and carbohydrate, and was isocaloric to the habitual diets.

Figure 1
figure1

Dietary protocol for the study.

The MUFA and HCLF diets were designed to have a similar carotenoid content, with high lycopene. The sources of lycopene were 300 g tomato soup (ready to serve) and 60 g of tomato paste every day. To avoid any seasonal and processing variations that might affect the carotenoid content of the food (Stahl & Sies, 1992; Lessin et al, 1997; Schierle et al, 1997), single batches of tomato soup and tomato paste, provided by HJ Heinz Australia (Melbourne, Australia), were used. Portions of tomato paste were given to the subjects with recipes and instructions on cooking. Subjects were asked to cook batches of dishes for the duration of the dietary period, portion and freeze them at −20°C. Special instructions were given on the cooking time for the tomato paste and heating of the tomato soup, as the intensity and duration of cooking may affect the isomerisation of lycopene and other carotenoids (Khachik et al, 1992; Stahl & Sies, 1992; Lessin et al, 1997; Schierle et al, 1997). On both the diets, tomato paste was cooked with oil from the daily allowance. Subjects were given instructions to transfer one portion of tomato dish from the freezer to the fridge the night before use, and to the microwave for 2 min before consumption.

In order to control other carotenoid intake, a limited amount and variety of fruits (an apple or a banana every day) and vegetables (iceberg lettuce, cucumber and mushrooms for lunch and onion, 100 g of frozen peas and corn mix for the evening meal every day) were allowed on the two diets. Subjects were also instructed to use the same appliances and bowls for cooking and heating foods in the two dietary periods. This study design ensured that each subject consumed comparable amounts of lycopene and other carotenoids on the two diets.

An oleate-enriched variant of sunflower oil (Sunola™ oil) was used for the MUFA diet. The composition of monounsaturated fat in Sunola™ oil is 77.8%, compared to 19.5% in conventional sunflower oil (eg Crisco oil), the oil used for the HCLF dietary period. Meadow Lea Foods Ltd (Mascot, Australia) provided the cooking oil and margarine (from single batches) for the study. The diets were designed to provide 36–38% of energy from fat in the MUFA diet (approximately 68% of fat from monounsaturated fat) and 16–18% of energy from fat in the HCLF diet. The carbohydrate content of the two diets was designed to be 42 and 64% of energy in the MUFA and the HCLF diets, respectively. The protein content of both the diets was designed to be 15–18% of the total energy. The diets were designed to have similar contents of dietary cholesterol, fibre, and vitamin C and carotenoids.

The energy balance of the diets was maintained by using non-carotenoid-containing foods such as white bread, carbonated beverages and polyjoule (Nutricia, Australia) in the HCLF diet. Polyjoule is a glucose polymer containing maltodextrin and it provides 1615 kJ per 100 g. Toasted muesli and biscuits made with Sunola™ oil were included in the MUFA diet to provide the necessary amount of monounsaturated fat.

To increase compliance, highly motivated people were selected for the study and were given clear written and verbal instructions. The participants understood the importance of adhering to the diet. The standardised breakfast cereal, tomato products, cooking oil, margarine, biscuits and polyjoule were also provided for the dietary periods. Regular phone calls were made to subjects every second or third day to check compliance and any problems in adhering to the prescribed diets. At the end of the two dietary periods, subjects completed a 4-day diet record, which was used to analyse their nutrient intake and compliance.

Blood collection and analysis

Fasting venous blood samples were taken on days 1 and 15 of the two dietary periods. All subjects were asked to fast for 10–12 h, during which only drinking water was allowed. Venous blood samples were collected between 07.30 and 09.30. To reduce stress effects, subjects were made to rest for 10 min after arriving at the university before the blood sample was taken. For serum separation, the blood was allowed to coagulate for 1 h (protected from natural light) and then centrifuged at 3000 rpm at 4°C for 20 min. Serum was aliquotted and stored at −70°C for later analysis. All biochemical analyses were subsequently carried out in the same run to reduce inter-assay variability.

Biochemical analysis

Serum carotenoids

A high-pressure liquid chromatography (HPLC) method (Su et al, 1999) was used for the analysis of serum carotenoids. Serum samples that had been stored at −70°C were thawed to room temperature in the dark. All the samples were analysed in the dark under red light. A total of 200 μl of internal standard containing alpha-tocopherol acetate and retinyl acetate in 95% ethanol solution were added to 200 μl of the serum sample and vortexed for 1 min, to denature the proteins. Then 1 ml of hexane was added and the sample was vortexed for 1 min. To separate the phase containing all the carotenoids and tocopherols, the sample was centrifuged at 2500 rpm for 10 min, and the supernatant was separated and dried under nitrogen stream. The sample was reconstituted with 40 μl of chloroform, vortexed for 1 min and then 80 μl of acetonitrile:methanol was added and vortexed again for 1 min. The sample was then transferred to amber-coloured vials for analysis by HPLC.

The solvents used in mobile phase were acetonitrile/methanol/chloroform (45:45:10, v/v/v) containing 0.05% ammonium acetate in methanol, and 0.1% triethylamine in the acetonitrile at the flow rate of 1 ml/min. A 50 μl injection of the sample was used for the carotenoid and tocopherol analysis. Carotenoids were monitored at 450 nm, and tocopherols at 292 nm.

Food lycopene content

The tomato soup and tomato paste used for the study were also analysed for their lycopene content using HPLC. Briefly, 1 ml of internal standard (β-apo-8-carotenal in hexane with 0.01% of BHT) was added to 1 g of homogenised food sample, followed by magnesium carbonate and chloroform:methanol (2:1; 10 ml) containing 0.01% BHT. After 30 min, the extract was filtered under suction and the solid material was extracted repeatedly with chloroform:methanol (2:1, 10 ml) until the resulting filtrate was colourless. Water-soluble material was removed using a separation funnel. The organic phase was collected, dried over anhydrous sodium sulphate and then the solution was dried under nitrogen. The residue was reconstituted with 200 μl of solvent acetonitrile/methanol/chloroform (70:70:60 μl). The reconstituted sample was then transferred to amber vials and analysed by HPLC. In all, 10 and 50 μl of each sample were injected and the results obtained with the higher resolution were used for analysis.

Lipids and lipoproteins

Fasting serum total cholesterol and triglycerides and HDL cholesterol were measured on a centrifugal autoanalyser (Hitachi Boehringer Mannhein Automatic Analyser 704, Japan) using commercially available enzymatic calorimetric kits (Boehringer Mannhein, Melbourne, Australia). LDL cholesterol was calculated using the Friedewald formula (Friedewald et al, 1972). The ratio of LDL to HDL cholesterol was also calculated.

Statistical analysis

Statistical package for social scientists (SPSS, version 9, 1999, Chicago, USA) was used for the analysis of all the data obtained. The data were first assessed for normality of distribution, and log transformation was performed on non-normally distributed data (lipids, lipoproteins and carotenoids). Non-parametric tests were performed if the data were not normally distributed even after log transformation. All data are presented as mean±standard deviation (s.d.). A P-value of <0.05 was taken as statistically significant. Separate analysis by order was also undertaken using nonparametric tests. Mann–Whitney U-test was used to analyse the results of the whole group compared by order of dietary period.

Results

Seven subjects commenced on the MUFA diet and six subjects commenced on the HCLF diet. All subjects completed the two dietary periods. The mean (±s.d.) age and BMI of the subjects at baseline were 39±11 y and 25.5±2.4 kg/m2, respectively.

Diets

The nutrient intakes of the study group calculated from the 4-day food records collected at the end of the two dietary periods are presented in Table 1. Energy intake on the MUFA diet was significantly higher than on the HCLF diet. There was no difference in the grams of protein consumed, but the percentage of energy provided by protein was significantly higher on the HCLF diet compared to the MUFA diet. As designed, the carbohydrate, total sugar and starch intake were higher and the total fat intake was lower on the HCLF diet.

Table 1 Average nutrient intake on HCLF and MUFA dieta,b (N=13)

The total fat intake on the MUFA diet was 2.6 times higher than on the HCLF diet. The polyunsaturated-to-saturated-fat ratio was 0.93 on both the diets, although the grams of polyunsaturated fat and saturated fat were higher on the MUFA diet compared to the HCLF diet. Monounsaturated fat intake was significantly higher (about six times) on the MUFA diet compared to the HCLF diet. The intake of alcohol, fibre, dietary cholesterol and vitamin C was similar on the two diets. The lycopene intake during the two dietary periods was 20.2 mg per day as analysed by HPLC in duplicate, and 28.2 mg per day as calculated from the USDA database (USDA, 1998).

The vitamin E content of the diets was different because of the different types and amounts of oils used. The MUFA diet provided 26.98 mg/day alpha-tocopherol and 0.24 mg/day gamma-tocopherol and the HCLF diet provided 2.62 mg/day alpha-tocopherol and 0.03 mg/day gamma-tocopherol. It would have been difficult to control for differences between the two diets unless supplements of different nutrients had been allowed, which would have changed the present study design.

Serum carotenoids

As serum carotenoid and alpha-tocopherol concentrations are thought to be associated with serum lipid concentrations, serum carotenoids were adjusted for total cholesterol in one analysis. However, this did not change any results, and the unadjusted data are presented. The baseline serum carotenoid and alpha-tocopherol concentrations measured at the beginning of the two 14 day dietary periods were similar (Table 2), suggesting the 42 day washout period was sufficient.

Table 2 Serum concentration of alpha-tocopherol and carotenoidsa

Both diets resulted in a significant increase in the serum trans, cis and total lycopene levels compared to the baseline. The increase in serum total, trans and cis lycopene from baseline to day 15 on the HCLF was 108, 114 and 106%, respectively. On the MUFA diet, the increase in the serum total, trans and cis lycopene levels was 126, 119 and 141%. Serum lutein+zeaxanthin, beta-carotene and alpha-tocopherol did not change significantly from the baseline to day 15 on both the diets. Cryptoxanthin and alpha-carotene were reduced on both the diets. The reduction in cryptoxanthin was 25% on the HCLF diet and 27% on the MUFA diet. Alpha-carotene decreased by 25% on the HCLF diet and by 43% on the MUFA diet. Serum cryptoxanthin and alpha-carotene were also adjusted for serum triglyceride levels; however, no change in the results was noted.

Comparing day 15 of both the two diets and also the change over the two dietary periods, there was no significant difference for any of the carotenoid levels for the group as a whole. The day 15 data were also analysed (Table 3) to determine if the order in which the diets were given (HCLF then MUFA or MUFA then HCLF) resulted in any significant difference in carotenoid levels. The day 15 data were also analysed to check for any difference in results within each dietary group, that is, MUFA first compared to MUFA second; HCLF first compared to HCLF second. No significant difference was noted in either case (Table 3).

Table 3 Serum concentration of alpha-tocopherol and carotenoids on day 15 by dietary order and perioda

Cholesterol and lipids

Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and LDL-to-HDL ratio were not significantly different at the start (baseline) of the two dietary periods (Table 4). Intervention diets for 2 weeks resulted in a significant decrease in the total cholesterol (13% on HCLF and 14% on MUFA) and LDL cholesterol (18% on HCLF and 17% on MUFA) from baseline. HDL cholesterol fell significantly by 10% on the HCLF diet but no change was noted on the MUFA diet. There was no significant change in LDL-to-HDL cholesterol ratio from baseline to day 15 of the two diets. Serum triglyceride levels increased on the HCLF diet by 19%, whereas no change was observed on the MUFA diet.

Table 4 Serum lipids and lipoproteinsa (N=13)

Comparing the end (day 15) of the two diets, there was no significant difference between serum total cholesterol or LDL cholesterol levels. HDL cholesterol was significantly higher (mean difference 0.17 mmol/l, P<0.01) at the end of the MUFA diet compared to the HCLF diet, and the LDL-to-HDL cholesterol ratio was lower (mean difference −0.42, P=0.02) at the end of the MUFA diet. Triglycerides were significantly lower (mean difference −0.40 mmol/l, P<0.01) at end of the MUFA diet compared to the HCLF diet.

Discussion

The main aim of this randomised crossover dietary intervention study was to compare the effects of two diets with similar carotenoid contents but markedly different fat intake (15% of energy from fat and 38% of energy mainly from monounsaturated fat) on the serum lycopene levels.

The results suggest that 15 or 38% of energy from fat in the diet has no major differential effect on serum lycopene in men with a high lycopene intake. Other carotenoids and alpha-tocopherol levels also indicate no major differential effect, although the large s.d.s mean that small differences cannot be excluded. Previous studies that suggested a significant role of fat in the bioavailability of beta-carotene had compared no fat meals with meals cooked in fat (Dimitrov et al, 1988; Prince & Frisoli, 1993). Also, these studies were of short duration — 5 days (Dimitrov et al, 1988) or a single dose test (Prince & Frisoli, 1993). It is possible that fat may have an effect on the serum concentration of carotenoids but only for a short duration of time, with less effect over longer periods. A 7-day study compared high intake of alpha- and beta-carotene, alpha-tocopherol or lutein/zeaxanthin with 3 g of dietary fat per day or 36 g dietary fat per day (Roodenburg et al, 2000). No effect on serum alpha- and beta-carotene with increased intake of alpha- and beta-carotene was seen. However, a difference in serum lutein levels was observed after a 7-day diet of high dietary intake of lutein with 3 g or 36 g of fat. This result was attributed to the form (esterified) in which lutein was ingested as it is more lipophilic than free lutein from vegetables like spinach and broccoli. Two longer term studies (3–4 weeks) that noted the effect of dietary fat on serum beta-carotene and vitamin A levels, in preschool and school children, suggested that the threshold level needed for intestinal carotene uptake lies between 3 and 5 g of fat (Jayarajan et al, 1980; Jalal et al, 1998) as no further increase was seen while comparing the effect of a carotenoid-rich meal cooked with 5 and 10 g of fat.

The effects of a controlled fat diet (43% of energy) in free-living adults were compared with a reduced fat (35% of energy) diet on the serum levels of fat-soluble vitamins and carotenoids over a period of 6 months (Velthuis te Wierik et al, 1996). The carotenoid intake was not checked/controlled; however, the researchers assumed that it was similar. The serum alpha-tocopherol levels were similar after 6 months of the diets even though the ‘somewhat’ reduced fat diet was low in dietary alpha-tocopherol, suggesting that over long periods of time the utilisation of alpha tocopherol may decrease with lower intake but serum levels stay the same. There were no differences in serum lycopene and beta-carotene levels after the controlled or reduced fat diet, but the difference in fat intake was small and the lower fat diet still contained a considerable amount of fat. The World Health Organization recommends that fat intake should not be below 15% of energy, to avoid highly bulky diets with inadequate energy intake (WHO, 1990). It is possible that even less than 15% of energy from fat is required to see a difference. However, for the present investigation, 15 and 38% of energy were used, as these extremes are feasible and not too difficult to adhere to.

Moderate alterations in the diet over short periods of time are known to change the measurable carotenoids in the human serum (Rock et al, 1992; Yeum et al, 1996; Lee et al, 2000). In the present study, both HCLF and MUFA diets caused an increase in the serum total, cis and trans lycopene levels, no change in lutein+zeaxanthin, beta-carotene and a decrease in alpha-carotene and cryptoxanthin levels compared to the baseline. These results would seem to reflect the good dietary compliance. The study diets were high in lycopene (28.2 mg/day) with little beta-carotene and lutein+zeaxanthin (1.20 and 1.50 mg/day) and minimal alpha-carotene and cryptoxanthin (0.04 and 0 mg/day). It is likely that the group's intake of lycopene during the intervention period was higher than on their habitual diets and the intake of alpha-carotene and cryptoxanthin was lower than on their habitual diets. The habitual carotenoid intake was not measured as it would have required specific information on fruit and vegetable intake from food frequency questionnaires or at least seven days of weighed food records (Block, 1982; Bingham, 1991) on all the subjects with comparable data during the study diets. This limits our ability to interpret the comparison accurately.

Another possible explanation for the results is an interaction between the carotenoids (Micozzi et al, 1992; Johnson et al, 1997). However, there is no indication from the literature that lycopene affects the absorption of alpha-carotene or cryptoxanthin. In fact, it has been suggested that cryptoxanthin is not affected by other carotenoid intake (Bowen et al, 1993; Yeum et al, 1996). The present investigation involved considerable manipulation of the diet (high lycopene, low in other carotenoids and different fat contents). It is thus hard to determine if the effect on the other serum carotenoid levels was because of the controlled/low intake of these carotenoids, the high lycopene intake, the fat content of the diet or a combination of these factors. A limitation of the study protocol is that the possible effects of the different components of the diets cannot be differentiated.

Stahl and Sies (1992) found that the serum cis lycopene levels were higher compared to the trans lycopene after 4 days of consumption of tomatoes. However, in our study no significant change in the plasma trans:cis ratio was observed, suggesting similar absorption of the two isomers over two weeks of high lycopene consumption (Olmedilla et al, 2002).

A secondary study aim was a comparison of the effects of the diets on serum lipids and lipoprotein levels. The energy intake on the MUFA diet was higher than the HCLF diet, mainly because of two or three subjects with particularly high intakes on the MUFA diet, but this difference was not reflected by body weight change. It is assumed that the large difference in monounsaturated fat intake between the two diets (20%) was the major factor influencing the lipid results, rather than the minor differences in polyunsaturated fat (0.5%) and saturated fat (0.3%) intake. The results confirmed those from other studies that both MUFA and HCLF diets reduce serum total cholesterol and LDL cholesterol (Garg et al, 1988; Grundy et al, 1988; Ashton et al, 2001). A high dietary intake of lycopene decreases serum cholesterol levels (Fuhrman et al, 1997), but lycopene intake was the same on the two diets; therefore, we cannot evaluate whether the observed changes in serum cholesterol were due to an individual or combined effect of lycopene intake and the study diets. The reported effect on serum HDL cholesterol and serum triglyceride levels are variable (Garg et al, 1988; Grundy et al, 1988; Berry et al, 1992; Ashton et al, 2001), but the present investigation showed a higher serum HDL cholesterol level on the MUFA diet, as found by Garg et al (1988) and Grundy et al (1988) and lower serum triglycerides, as found by Berry et al (1992) and Garg et al (1988). Dietary factors like fibre, total sugar and starch may affect the fasting triglyceride levels. In the present investigation, the fibre intake was similar, but total sugar and starch intake was higher on the HCLF diet, which may have increased serum triglycerides by increasing hepatic synthesis. Also, if a higher LDL-to-HDL ratio depicts a higher risk of CHD (LaRosa et al, 1990; Despres et al, 2000), then the results of this investigation suggest that a MUFA diet may have a better impact in reducing CHD risk.

The present study was conducted only in men, but it adds to the existing knowledge on carotenoids and encourages further research to extend the results of this investigation. A larger study sample would be needed to be powerful enough to exclude any small effect on the other carotenoids specifically owing to the difference in fat component. Studies of different design are needed to further determine the interaction of dietary factors and serum levels of the different carotenoids and to explore the effects in women. As the optimum serum levels of lycopene and other carotenoids are unknown, more research is required in both men and women to evaluate the relation between dietary lycopene, serum lycopene and the prevention of chronic diseases such as CHD, by long-term intervention trials using a variety of food products.

In conclusion, the present study suggests that 15 or 38% of dietary energy from fat does not have a significant differential effect on serum lycopene levels in men on a high-lycopene, low-carotenoid diet. In all, 15% of energy from fat may be enough to ensure absorption of lycopene and more fat may not increase the absorption. However, the intake of lycopene-rich foods cooked with monounsaturated fat may have an added benefit against CHD.

References

  1. Ashton EL, Best JD &, Ball MJ (2001): Effects of monounsaturated enriched sunflower oil on CHD risk factors including LDL size and copper-induced LDL oxidation. J. Am. Coll. Nutr. 20, 320–326.

    CAS  Article  Google Scholar 

  2. ATBC (1994): The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N. Engl. J. Med. 330, 1029–1035.

  3. Berry EM, Eisenberg S, Friedlander Y, Harats D, Kauftnann NA, Norman Y &, Stein Y (1992): Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins—the Jerusalem Nutrition Study. II. Monounsaturated fatty acids vs carbohydrates. Am. J. Clin. Nutr. 56, 394–403.

    CAS  Article  Google Scholar 

  4. Bingham SA (1991): Limitations of the various methods for collecting dietary intake data. Ann. Nutr. Metab. 35, 117–127.

    CAS  Article  Google Scholar 

  5. Block G (1982): A review of validations of dietary assessment methods. Am. J. Epidemiol. 115, 492–505.

    CAS  Article  Google Scholar 

  6. Bowen PE, Garg V, Stacewicz Sapuntzakis M, Yelton L &, Schreiner RS (1993): Variability of serum carotenoids in response to controlled diets containing six servings of fruits and vegetables per day. Ann. N Y Acad. Sci. 691, 241–243.

    CAS  Article  Google Scholar 

  7. Chasan-Taber L, Willett WC, Seddon JM, Stampfer MJ, Rosner B, Colditz GA, Speizer FE &, Hankinson SE (1999): A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am. J. Clin. Nutr. 70, 509–516.

    CAS  Article  Google Scholar 

  8. Clarke R (1997): Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ 314, 112–117.

    CAS  Article  Google Scholar 

  9. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J &, Mamelle N (1999): Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 99, 779–785.

    CAS  Article  Google Scholar 

  10. Despres JP, Lemieux I, Dagenais GR, Cantin B &, Lamarche B (2000): HDL-cholesterol as a marker of coronary heart disease risk: the Quebec cardiovascular study. Atheroselerosis 153, 263–272.

    CAS  Article  Google Scholar 

  11. Di Mascio P, Kaiser S &, Sies H (1989): Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch. Biochem. Biophys. 274, 532–538.

    CAS  Article  Google Scholar 

  12. Dimitrov NV, Meyer C, Ullrey DE, Chenoweth W, Michelakis A, Malone W, Boone C &, Fink G (1988): Bioavailability of beta-carotene in humans. Am. J. Clin. Nutr. 48, 298–304.

    CAS  Article  Google Scholar 

  13. D'Odorico A, Martines D, Kiechl S, Egger G, Oberhollenzer F, Bonvicini P, Sturniolo GC, Naccarato R &, Willeit J (2000): High plasma levels of alpha- and beta-carotene are associated with a lower risk of atherosclerosis: results from the Bruneck study. Atherosclerosis 153, 231–239.

    CAS  Article  Google Scholar 

  14. Elinder LS, Hadell K, Johansson L, Holme JM, Olsson AG &, Walldius G (1995): Probucol treatment decreases serum concentration of diet-derived antioxidants. Arterioscler. Thromb. Vasc. Biol. 15, 1057–1631.

    CAS  Article  Google Scholar 

  15. Forman MR, Beecher GR, Lanza E, Reichman ME, Graubard BI, Campbell WS, Marr T, Yong LC, Judd JT &, Taylor PR (1995): Effect of alcohol consumption on plasma carotenoid concentrations in premenopausal women: a controlled dietary study. Am. J. Clin. Nutr. 62, 131–135.

    CAS  Article  Google Scholar 

  16. Friedewald WT, Levy RI &, Fredrickson DS (1972): Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502.

    CAS  PubMed  Google Scholar 

  17. Fuhrman B, Elis A &, Aviram M (1997): Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages. Biochem. Biophys. Res. Commun. 233, 658–662.

    CAS  Article  Google Scholar 

  18. Garg A, Bonanome A, Grundy SM, Zhang ZJ &, Unger RH (1988): Comparison of a high-carbohydrate diet with a high-monoun-saturated-fat diet in patients with noninsulin-dependent diabetes mellitus. N. Engl. J. Med. 319, 829–834.

    CAS  Article  Google Scholar 

  19. Giovannucci E, Ascherio A, Rimm EB, Stampfer ML, Colditz GA &, Willett WC (1995): Intake of carotenoids and retinol in relation to risk of prostate cancer. J. Natl. Cancer Inst. 87, 1767–1776.

    CAS  Article  Google Scholar 

  20. Grundy SM, Florentin L, Nix D &, Whelan MF (1988): Comparison of monounsaturated fatty acids and carbohydrates for reducing raised levels of plasma cholesterol in man. Am. J. Clin. Nutr. 47, 965–969.

    CAS  Article  Google Scholar 

  21. Haskell WL, Alderman EL, Fair JM, Maron DJ, Mackey SF, Superko HR, Williams PT, Johnstone IM, Champagne MA &, Krauss RM (1994): Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. The Stanford Coronary Risk Intervention Project (SCRIP). Circulation 89, 975–990.

    CAS  Article  Google Scholar 

  22. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, Belanger C, LaMotte F, Gaziano JM, Ridker PM, Willett W &, Peto R (1996): Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N. Engl. J. Med. 334, 1145–1149.

    CAS  Article  Google Scholar 

  23. Jacques PF &, Chylack Jr LT (1991): Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention. Am. J. Clin. Nutr. 53, 352S–355S.

    CAS  Article  Google Scholar 

  24. Jalal F, Nesheim MC, Agus Z, Sanjur D &, Habicht JP (1998): Serum retinol concentrations in children are affected by food sources of beta-carotene, fat intake, and anthelmintic drug treatment. Am. J. Clin. Nutr. 68, 623–629.

    CAS  Article  Google Scholar 

  25. Jayarajan P, Reddy V &, Mohanram M (1980): Effect of dietary fat on absorption of beta carotene from green leafy vegetables in children. Indian J. Med. Res. 71, 53–56.

    CAS  PubMed  Google Scholar 

  26. Johnson EJ, Qin J, Krinsky NI &, Russell RM (1997): Ingestion by men of a combined dose of beta-carotene and lycopene does not affect the absorption of beta-carotene but improves that of lycopene. J. Nutr. 127, 1833–1837.

    CAS  Article  Google Scholar 

  27. Katan MB, Grundy SM &, Willett WC (1997): Should a low-fat, high-carbohydrate diet be recommended for everyone? Beyond low-fat diets. N. Engl. J. Med. 337, 563–566.

    CAS  PubMed  Google Scholar 

  28. Khachik R, Beecher GR, Goli MB, Lusby WR &, Smith Jr JC (1992): Separation and identification of carotenoids and their oxidation products in the extracts of human plasma. Anal. Chem. 64, 2111–2122.

    CAS  Article  Google Scholar 

  29. Klipstein Grobusch K, Launer LJ, Geleijnse JM, Boeing H, Hofman A &, Witteman JC (2000): Serum carotenoids and atherosclerosis. The Rotterdam Study. Atherosclerosis 148, 49–56.

    CAS  Article  Google Scholar 

  30. Kostic D, White WS &, Olson JA (1995): Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses. Am. J. Clin. Nutr. 62, 604–610.

    CAS  Article  Google Scholar 

  31. Kromhout D (1989): Food consumption patterns in the Seven Countries Study. Seven Countries Study Research Group. Ann. Med. 21, 237–238.

    CAS  Article  Google Scholar 

  32. LaRosa JC, Hunninghake D, Bush D, Criqui MH, Getz GS, Gotto AM, Grundy SM, Rakita L, Robertson RM, Weisfeldt ML et al (1990): The cholesterol facts. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. A joint statement by the American Heart Association and the National Heart, Lung, and Blood Institute. The Task Force on Cholesterol Issues, American Heart Association. Circulation 81, 1721–1733.

    CAS  Article  Google Scholar 

  33. Le Marchand L, Hankin JH, Kolonel LN, Beecher GR, Wilkens LR &, Zhao LP (1993): Intake of specific carotenoids and lung cancer risk. Cancer Epidemiol. Biomarkers Prev. 2, 183–187.

    CAS  PubMed  Google Scholar 

  34. Lee A, Thurnham DI &, Chopra M (2000): Consumption of tomato products with olive oil but not sunflower oil increases the antioxidant activity of plasma. Free Rad. Biol. Med. 29, 1051–1055.

    CAS  Article  Google Scholar 

  35. Lessin W, Catigani G &, Schwartz S (1997): Quantification of cis-trans isomers of provitamin A carotenoids in fresh fruits and vegetables. J. Agric. Food Chem. 45, 3728–3732.

    CAS  Article  Google Scholar 

  36. Mensink RP &, Katan MB (1992): Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler. Thromb. 12, 911–919.

    CAS  Article  Google Scholar 

  37. Michaud DS, Feskanich D, Rimm EB, Colditz GA, Speizer FE, Willett WC &, Giovannucci E (2000): Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am. J. Clin. Nutr. 72, 990–997.

    CAS  Article  Google Scholar 

  38. Micozzi MS, Brown ED, Edwards BK, Bieri JG, Taylor PR, Khachik F, Beecher GR &, Smith Jr JC (1992): Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men. Am. J. Clin. Nutr. 55, 1120–1125.

    CAS  Article  Google Scholar 

  39. Miller NJ, Sampson J, Candeias LP, Bramley PM &, Rice-Evans CA (1996): Antioxidant activities of carotenes and xanthophylls. FEBS Lett. 384, 240–242.

    CAS  Article  Google Scholar 

  40. Mortensen A, Skibsted LH, Sampson L, Rice Evans C &, Everett SA (1997): Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants. FEBS Lett. 418, 91–97.

    CAS  Article  Google Scholar 

  41. Norrish AE, Jackson RT, Sharpe SJ &, Skeaff CM (2000): Prostate cancer and dietary carotenoids. Am. J. Epidemiol. 151, 119–123.

    CAS  Article  Google Scholar 

  42. Olmedilla Alonso B, Granado Lorencio R, Gil Martinez E, Blanco Navarro I &, Rojas Hidalgo E (1997): Serum status of carotenoids in control subjects and its relation to the diet. Nutr. Hosp. 12, 245–249.

    CAS  PubMed  Google Scholar 

  43. Olmedilla B, Granado F, Blanco I &, Rojas Hidalgo E (1994): Seasonal and sex-related variations in six serum carotenoids, retinol, and alpha-tocopherol. Am. J. Clin. Nutr. 60, 106–110.

    CAS  Article  Google Scholar 

  44. Olmedilla B, Granado F, Southon S, Wright AJA, Blanco I, Gil-Martinez E, van den Berg H, Thurnham D, Corridan B, Chopra M &, Hininger I (2002): A European multicentre, placebo-controlled supplementation study with alpha-tocopherol, carotene-rich palm oil, lutein or lycopene: analysis of serum responses. Clin. Sci. 102, 447–456.

    CAS  Article  Google Scholar 

  45. Omenn GS, Goodman GE, Thonquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Bamhart S &, Hammar S (1996): Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med. 334, 1150–1155.

    CAS  Article  Google Scholar 

  46. Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Annstrong WT, Ports TA, Kirkeeide RL, Hogeboom C &, Brand RJ (1998): Intensive lifestyle changes for reversal of coronary heart disease. JAMA 280, 2001–2007.

    CAS  Article  Google Scholar 

  47. Paiva SA &, Russell RM (1999): Beta-carotene and other carotenoids as antioxidants. J. Am. Coll. Nutr. 18, 426–433.

    CAS  Article  Google Scholar 

  48. Parks EJ &, Hellerstein MK (2000): Carbohydrate-induced hypertri-acylglycerolemia: historical perspective and review of biological mechanisms. Am. J. Clin. Nutr. 71, 412–433.

    CAS  Article  Google Scholar 

  49. Porrini M, Riso P &, Testolin G (1998): Absorption of lycopene from single or daily portions of raw and processed tomato. Br. J. Nutr. 80, 353–361.

    CAS  Article  Google Scholar 

  50. Prince MR &, Frisoli JK (1993): Beta-carotene accumulation in serum and skin. Am. J. Clin. Nutr. 57, 175–181.

    CAS  Article  Google Scholar 

  51. Rissanen TH, Voutilainen S, Nyyssorien K, Lakka TA, Sivenius J, Salonen R, Kaplan GA &, Salonen JT (2001): Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study. Br. J. Nutr. 85, 749–754.

    CAS  Article  Google Scholar 

  52. Rock CL, Swendseid ME, Jacob RA &, McKee RW (1992): Plasma carotenoid levels in human subjects fed a low carotenoid diet. J. Nutr. 122, 96–100.

    CAS  Article  Google Scholar 

  53. Roodenburg AJ, Leenen R, van het Hof KH, Weststrate JA &, Tijburg LB (2000): Amount of fat in the diet affects bioavailability of lutein esters but not of alpha-carotene, beta-carotene, and vitamin E in humans. Am. J. Clin. Nutr. 71, 1187–1193.

    CAS  Article  Google Scholar 

  54. Schierle L, Bretzel W, Buehler I, Faccin N, Hess D, Steiner K &, Schueep W (1997): Content and isomeric ratio of lycopene in food and human blood plasma. Food Chem. 59, 459–465.

    CAS  Article  Google Scholar 

  55. Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, Haller J, Miller DT et al. (1994): Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration Eye Disease Case-Control Study Group. JAMA 272, 1413–1420.

    CAS  Article  Google Scholar 

  56. Stahl W &, Sies H (1992): Uptake of lycopene and its geometrical isomers is greater from heat-processed than from unprocessed tomato juice in humans. J. Nutr. 122, 2161–2166.

    CAS  Article  Google Scholar 

  57. Street DA, Comstock GW, Salkeld RM, Schuep W &, Klag MJ (1994): Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction? Circulation 90, 1154–1161.

    CAS  Article  Google Scholar 

  58. Su Q, Rowley KG &, O'Dea K (1999): Stability of individual carotenoids, retinol and tocopherols in human plasma during exposure to light and after extraction. J. Chromatogr. B. Biomed. Sci. Appl. 729, 191–198.

    CAS  Article  Google Scholar 

  59. USDA (1998): USDA-NCC Carotenoid Database for US Foods: National Cancer Institute. http://www.nal.usda.gov/fnic/foodcomp/Data/car98/car98.html.

  60. Velthuis te Wierik EJ, van den Berg H, Weststrate JA, van het Hof KH &, de Graaf C (1996): Consumption of reduced-fat products: effects on parameters of antioxidative capacity. Eur. J. Clin. Nutr. 50, 214–219.

    CAS  PubMed  Google Scholar 

  61. Watts GF, Lewis B, Brunt JN, Lewis ES, Coltart DJ, Smith LD, Mann JI &, Swan AV (1992): Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas'Atherosclerosis Regression Study (STARS). Lancet 339, 563–569.

    CAS  Article  Google Scholar 

  62. Wei W, Kim Y &, Boudreau N (2001): Association of smoking with serum and dietary levels of antioxidants in adults: NHANES III, 1988-1994. Am. J. Public Health 91, 258–264.

    CAS  Article  Google Scholar 

  63. WHO (1990): Diet, nutrition and the prevention of chronic diseases. Geneva: WHO.

  64. Williams AW, Boileau TW &, Erdman Jr JW (1998): Factors influencing the uptake and absorption of carotenoids. Proc. Soc. Exp. Biol. Med. 218, 106–118.

    CAS  Article  Google Scholar 

  65. Yeum KJ, Booth SL, Sadowski JA, Liu C, Tang G, Krinsky NI &, Russell RM (1996): Human plasma carotenoid response to the ingestion of controlled diets high in fruits and vegetables. Am. J. Clin. Nutr. 64, 594–602.

    CAS  Article  Google Scholar 

  66. Zeegers MP, Goldbohm RA &, van den Brandt PA (2001): Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk? Results from the Netherlands Cohort Study. Br. J. Cancer. 85, 977–983.

    CAS  Article  Google Scholar 

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Acknowledgements

Dr Su Qing for performing the biochemical analysis of carotenoids.

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Guarantor: M Ball

Contributors: KA was involved in the design, subject recruitment, conduct of the study, dietary and laboratory analysis, statistical analyses and writing of the paper. EA was involved in the day-to-day running and laboratory analysis of the study. MB was involved in the design of the study, supervision of the running of the study and writing of the paper.

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Correspondence to M J Ball.

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Ahuja, K., Ashton, E. & Ball, M. Effects of a high monounsaturated fat, tomato-rich diet on serum levels of lycopene. Eur J Clin Nutr 57, 832–841 (2003). https://doi.org/10.1038/sj.ejcn.1601617

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Keywords

  • monounsaturated fat
  • lycopene
  • carotenoids
  • dietary intervention

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