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Dr Arab: I can tell you how much lycopene was present in the body fat of those in the highest quintile, but I cannot tell you how much they ate. I could extrapolate from the concentration per gram of fat, their body fat content, and the lycopene content of tomatoes to estimate how much one would have to eat.
Dr Roberfroid: Why does absorption increase when the tomatoes are cooked?
Dr Arab: You have to break down the cell wall and the chromoplast; within that, lycopene is in a crystalline structure. Then, before it can be absorbed, it has to be in lipid form. So actually it has to be extracted from the food matrix.
We are contradicting the recommendation to eat fresh fruits and vegetables. We are also contradicting the recommendation to eat 5 fruits and vegetables of any type. Like the animals in Animal Farm, some fruits and vegetables are more equal than others. We really should increase the consumption of a few very important ones.
Dr Meydani: Have you looked at the correlation between the plasma level of lycopene and the adipose tissue level? Also, was there any kind of association between the lycopene level and the levels of other antioxidants such as tocopherol in adipose tissue?
Dr Arab: We did a parallel study [Kardinaal AF, van't Veer P, Brants HA, van den Berg H, van Schoonhoven J, Hermus J. Relations between antioxidant vitamins in adipose tissue, plasma, and dust. Am J Epidemiol 1995;141:440–50] in which we gave ß-carotene supplements over 6 mo and looked at changes in adipose tissue and serum. Also, we took samples in our control population and measured both serum and adipose tissue values. The correlation coefficients were 0.4 to 0.6. They differed for men and women and depended on smoking status.
When we use biomarkers, we need to consider what they represent. Serum represents intake for the last month or 2; adipose tissue represents intake for the last 2–5 y. These very different reference times have important implications on study design and the interpretation of results.
Dr Dwyer: Can you comment on ß-carotene and carotenoid absorption generally?
Dr Arab: It has been speculated that one problem with ß-carotene trials may be that when people consume a load of ß-carotene, lycopene absorption is suppressed [Su LC, Bui M, Kardinaal, et al. Differences between plasma and adipose tissue biomarkers of carotenoids and tocopherols. Cancer Epidemiol Biomarkers Prev 1998;7:1043–8]. That hasn't been confirmed, but the results are mixed. That doesn't seem to be the primary issue, however. There seems to be passive absorption through the gut into chylomicrons and then into the blood. From a load of ß-carotene, 95% is excreted and only 5% is absorbed unless measures are taken to increase absorption. If one eats carrots without dipping them in chocolate or salad dressing, the absorption rate may be zero.
Dr Green: The carotenoid lutein is a popular over-the-counter antioxidant. It is supposed to prevent macular degeneration. Is lutein the most abundant carotenoid in plants? Is lycopene a marker for luetin?
Dr Arab: No. Carotenoids are pigments; lutein is yellow, lycopene is red, ß-carotene is orange. Not many green food sources are also rich in lycopene. Lycopene is found almost exclusively in tomatoes.
Dr Crowell: Sies and colleagues [Stahl W, Schwarz W, Sundquist AR, Sies H. Cis-trans isomers of lycopene and beta-carotene in human serum and tissues. Arch Biochem Biophys 1992;294:173–7] looked at the distribution of lycopene in tissues in autopsy samples. I don't recall if cardiac tissue was specifically identified or whether you are thinking the effect is more in the cardiovascular system.
Dr Arab: He found very low levels in muscle tissues. He studied 20 cases at autopsy; 10 were from people who died from respiratory illnesses. We are trying to determine whether his observations lend support to our lycopene and lung hypothesis. Muscular tissue is not a good source. At least 70–80% of carotenoids, including lycopene and ß-carotene, are in adipose tissue.
We still do not know why certain tissues seem to accumulate lycopene and not ß-carotene, and why isomerization occurs in different tissues. We do not think lycopene accumulates in the heart.
Dr Milner: Why would gazpacho have so much more lycopene than tomato?
Dr Arab: Gazpacho is cold tomato soup, but why should its lycopene be higher than, for example, that of tomato juice?
Dr Dwyer: Because it's concentrated; in tomatoes, much of the water is removed, so that the concentration is increased.
Dr Milner: But this was on a per gram basis, was it not?
Dr Arab: Yes, per 100 g.
Dr Milner: Is there evidence that any of these carotenoids modify cyclooxygenase activity or prostaglandin biosynthesis?
Dr Arab: Not that I know of. The only other strong carotenoid effect that may have something to do with this is stimulation of connexin 43 through carotenoids, actually affecting gap junction channels [Bertram JS, Bortkiewicz H. Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells. Am J Clin Nutr 1995;62(suppl):1327S–36S].
Dr Weisburger: I was intrigued by body lycopene content being so high in Moscow. In Italy, they usually use olive oil with their cooked tomatoes. I wonder if, in Moscow and some other countries, you have high intake of fat and therefore this "drags" more carotenoids through the intestinal mucosa. Also, people who smoke induce enzymes, especially in the liver, where vitamin A, carotene, and lycopene are metabolized. Did you consider that smokers have differences in metabolism that may result in differences in distribution of some of these carotenoids?
Dr Arab: With regard to Moscow, your theory may be true. The fat content of the diet is very high. We were surprised with their results because tomatoes are extremely expensive there, but in summer many people grow their own, so there is a plausible source.
Dr Weisburger: Do they eat tomatoes raw or cooked in Moscow?
Dr Arab: Cooked. Fortunately, for our use of lycopene as a marker, lycopene, unlike ß-carotene, does not seem to be influenced by cigarette smoking. We have seen this in 2 other studies [Iribarren C, Folsom AR, Jacobs DR Jr, Gross MD, Belcher MD, Eckfeldt JH. Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control study. The ARIC Study Investigators. Atherosclerosis Risk in Communities. Arterioscler Thromb Vasc Biol 1997;17:1171–7; Gomez-Aracena J, Sloots L, Garcia-Rodriguez A, et al. Antioxidants in adipose tissue and myocardial infarction in a Mediterranean area. The EURAMIC Study in Malaga. Nutr Metab Cardiovasc Dis 1997;7:376–82], and we were looking at it ourselves because we thought isomerization of lycopene may be a function of cigarette smoking, but that is not panning out.
Returning to the question of vitamin E, we see no association between adipose tissue levels and serum levels. -Tocopherol in adipose tissue behaves strangely. There have been studies of supplementation for 1 y in which adipose tissue was continually monitored [Handelman GJ, Epstein WL, Peerson J, Spiegelman D, Machlin LJ, Dratz EA. Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation. Am J Clin Nutr 1994;59:1025–37]. Adipose tissue concentration of -tocopherol did not increase. Instead, there was a decrease in -tocopherol concentration.