Carotenoids and Lipid Peroxidation: Can Vegetables & Fruit Reduce ALEs?

Can we reduce ALEs by eating foods rich in carotenoids? (Photo by tibchris)

When you cook foods until they have that delicious brown color, what you're really seeing is advanced glycation end-products, or AGEs. In cooking, they're formed by heating sugars with fats or proteins, but they can also be formed inside the body through normal metabolism. The problem with AGEs is that with time, they accumulate in the body and cause harm.

Similar products are formed when polyunsaturated fats are oxidized, as a result of heating or contact with oxygen. These are known as advanced lipid peroxidation end-products, or ALEs. Lipid peroxidation is even more problematic than glycation, because it leads to ALEs much more rapidly than glycation leads to AGEs.

So what can we do to reduce the accumulation of ALEs? As we've seen, one obvious way is to avoid cooking with fats that contain lots of polyunsaturated fatty acids. Still, as in the case of AGEs, ALEs are formed not only on the frying pan but also inside the body as a result of metabolism. Since completely avoiding polyunsaturated fats is probably not feasible (and they may even have certain benefits), looking for ways to inhibit metabolic lipid peroxidation seems very useful.

In addition to fatty acids, other components of the diet play a role in the accumulation of AGEs and ALEs. One particular group of micronutrients that may be beneficial is carotenoids, the compounds which give vegetables and fruit their bright color. In this post, we'll take a look at what the studies say on carotenoids and lipid peroxidation.

Various carotenoids and lipid peroxidation

One study found that carotenoids inhibited lipid peroxidation in mouse embryo cells (link). The carotenoids tested were alpha-carotene, beta-carotene, canthaxanthin, lutein, lycopene, and bixin. Bixin, which is extracted from annatto seeds, was the most effective out of the six.

In another study, the effect of various carotenoids on lipid peroxidation were measured in membranes enriched with polyunsaturated fatty acids (link). Surprisingly, only astaxanthin reduced peroxide formation, while beta-carotene and lycopene increased it significantly. Zeaxanthin and lutein also increased peroxide formation slightly.

The authors of the second paper note that this may be because conventional antioxidant assays use high concentrations of free radicals over a period of a few hours, whereas this study observed the effects over a longer period (48 hours). The relevance to biological systems is not entirely clear, but these results might help explain some of the controversial effects of carotenoids (for example, beta-carotene increasing lung cancer risk in smokers).

Zooming in on lutein

While the above studies suggest that other carotenoids such as astaxanthin may be useful, many of the studies on lipid peroxidation focus mainly on lutein. One paper I've posted earlier about as part of my self-experiment claimed an improvement in skin elasticity, hydration and photoprotection from a supplement containing lutein. Interestingly, a reduction in lipid peroxidation was also seen.

In another study, when spinach or perilla preparations containing 5 mg lutein were given to healthy volunteers for 10 days, their plasma concentrations of lutein increased significantly (link). The increase was more pronounced after consumption of perilla, even though the amount of lutein in both preparations was the same. In other words, other micronutrients in the food in question have an effect on lutein absorption.

Glutathione peroxidase was unchanged, but superoxide dismutase increased slightly. Both of these enzymes protect the body from oxidative damage. As for lipid peroxidation, the concentration of malondialdehyde (MDA) in plasma tended to decrease and the time span until a rapid increase in oxidation (known as lag time) tended to increase after spinach and perilla. MDA is a product of lipid peroxidation which eventually forms ALEs.

It's interesting to note that while lutein is absorbed rather well from vegetable foods, it is also absorbed from carotenoid supplements. In fact, the bioavailability of lutein from vegetables is only 67% compared to a preparation of pure carotenoids (link). In contrast to some of the findings in other studies, in this study healthy volunteers fed a high-vegetable diet or given 9 mg lutein and 6 mg beta-carotene daily for 4 weeks did not show an increased resistance to LDL oxidation ex vivo. The authors suggest that one possible explanation is that while lutein and beta-carotene concentrations increased, plasma lycopene concentrations decreased on both diets.

In one human study on healthy men, subjects were first put on a low carotenoid diet and then given either 330 mL tomato juice, 330 mL carrot juice or 10 g spinach powder for 2 weeks to see how the diets affected LDL oxidation. This time it was tomato juice that reduced the lag time of lipoprotein oxidizability, while carrot juice and spinach powder had no effect (link). Glutathione peroxidase was again unchanged. Given that tomatoes contain both lutein and lycopene, perhaps this hints at some kind of a synergy between the two?

Finally, let's take a brief look at two studies suggesting that lutein might be useful in treating diseases related to lipid peroxidation.

Lipid hydroperoxides are non-radical intermediates of lipid peroxidation that are involved in many diseases. For example in dementia, the number of phospholipid hydroperoxides (PLOOH) in red blood cells is greatly increased. When six healthy subjects took 9.67 mg lutein daily for 4 weeks, PLOOH levels decreased in red blood cells (link). An antioxidant effect was confirmed in red blood cells but not in plasma.

Genetically modified mice (ApoE-/-) that have high cholesterol and develop atherosclerosis as a result. They also have increased levels of systemic and retinal lipid peroxidation compared to wild mice. Supplementing them with 0.09 mg/kg lutein per day protects their retinas from this oxidative damage (link), suggesting that lutein might be helpful for patients with hypercholesterolemia.

Conclusion

Carotenoids may be effective in reducing lipid peroxidation and thus the accumulation of ALEs. Lutein in particular seems useful: at doses of 5-10 mg per day, it has been shown to increase plasma levels of lutein and reduce some of the markers of lipid peroxidation. Other carotenoids, such as astaxanthin and bixin, may be beneficial as well.

It should be noted that some of the evidence is contradictory. Some studies have found no benefit, and one study even found a slight increase in lipid peroxidation from various carotenoids. A certain balance of carotenoids may be necessary for inhibiting the formation ALEs; lycopene in particular may be important.

For more information on AGEs, ALEs and aging, see these posts:

Sugar and AGEs: Fructose Is 10 Times Worse than Glucose
Eating Meat or Going Vegan? Comparing AGE Levels in Vegetarians and Omnivores
AGE Content of Foods
Green Tea Reduces the Formation of AGEs