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Unlike the pre-vitamin A carotenoids, lutein and zeaxanthin are absorbed and transported like other lipids. Briefly, lutein and zeaxanthin or their corresponding diesters are released from their food or supplement matrix. This first step may be extremely important and unfortunately continues to be ignored by many researchers. Bioavailability is affected by many factors, but the matrix it is presented in must address numerous stability issues and other factors that influence absorption. Some major issues that effect bioavailability include:
- Stability to digestive tract and storage conditions
- Binding by macromolecules like fiber and protein
- Presence or absence of fats and its ability to stimulate bile salts release and presence of pancreatic lipase
- Malnutrition factors
- Food processing to reduce particles size or mild heating to release xanthophylls from macromolecules or "cell wall trapping"
- Presence of competing carotenoids
It cannot be overstated how important bioavailability is to carotenoid nutrition. There are several reports of bioavailability of xanthophylls from both food matrixes and supplements of less than 5%. This means a consumer may believe they are ingesting 10 mg of lutein or zeaxanthin and actually only absorb 0.5 mg. For this reason it is important that you buy carotenoids for the eye from reputable companies.
The xanthophylls, upon release from the food/supplement matrix, are transferred to lipid micelles that contain other lipids and bile salts. The micelle is taken up by the intestinal mucosal cells and diffuses through cell membranes and is released to the other side of enterocytes. Esters of the xanthophylls are hydrolyzed by gut lipases and possibly at the intestinal lining. Because xanthophyll esters are hydrolyzed upon entering the intestine, nutritionists consider them equal on the actual mole/wt. basis. The free xanthophylls are transferred into chylomicrons and transported to the lymph system and with action of lipoprotein lipase are eventually taken up by the liver and are either stored or transferred to VLDL and then LDL and HDL particles. Xanthophylls are widely distributed among the lipoproteins and on the surface of these complexes where they may play an important role in protecting the lipoproteins from oxidation and subsequent atherosclerotic lesions.
Tissue Distribution. While the liver packages xanthophylls for blood transport, it is also a major deposition organ. The other major "sink for xanthophylls" is adipose (fat) tissue. Both tissues may "compete" with the eye for the xanthophylls. Several human surveys have demonstrated an inverse relationship between Body Mass Index (BMI) and lowered macular levels of pigment
Several animal studies and at least one human volunteer study have shown lutein to be deposited in adipose tissue greater than zeaxanthin, and there is a greater "retinal capture efficiency" for zeaxanthin over lutein (4:1). The xanthophylls also deposit broadly in many other organs but are particularly high in adrenal, kidney, breast, prostate, and eye.
Eye Tissues. The highest concentration of xanthophylls in the entire human body are in the macula region of the retina, in fact so high that they give this tissue its name macula lutea or yellow spot. These two xanthophylls are also found in the lens and Uveal bodies including ciliary body, iris, and, most importantly, the retinal pigment epithelium (RPE) and choroid. The levels in the macula are at 500-1,000 times greater in concentrations than any other tissue in the body. This very dramatic and compelling fact first grabbed scientists' attention and provides an intriguing hint that nature has a purpose for macular pigments in eye health. There is a 10-15 fold difference in human sub-populations in the natural concentrations of the macular pigment in the inner retinal layer (0.05 - 1.0 pmole/mm2). In the lens, the xanthophylls are about 10 times higher in the epithelial/cortical layer than the nuclear layer (44 vs. 4 ng/g lens wet weight). This represents orders of magnitude less than the retinal tissues.
Within the retina, a significant portion of the xanthophylls reside in the Henle's Fiber, a layer of axons in the inner retinal layer where xanthophylls can filter light prior to light striking photoreceptors (rods and cones) and the very important RPE cells. This location would suggest a strong role for the xanthophylls filtering damaging light (particularly the most damaging blue part of the spectrum). The xanthophylls are also found in the Rod Outer Segments suggesting a very strong membrane ordering and antioxidant role. Finally, the xanthophylls are found in the RPE cells where they may have multiple functions (see insert on eye anatomy).
The distribution of macular pigment is another strong biological hint that there is a role for xanthophylls in retinal health. As can be seen in Table 1 the macular pigment is highest in the exact center of the macula where dietary zeaxanthin and a related isomer, meso-zeaxanthin, dominate. In the peripheral retina, lutein dominates by 2-3 fold. The central sparing evident in AMD is the current theory that suggests that high macular pigment protects the portion of the macula with the highest exposure to photooxidative insult. Very high metabolic rates found in the fovea require extra antioxidant protection. AMD pathology often starts at the edges of the macula where macular pigment concentrations start to decrease. Analyses of cadaver eyes have shown this direct link by analyzing macular pigment concentrations at distances from the center of the macula between AMD eyes and normal control matched eyes. In these experiments, there is a significant drop in pigment concentration at the edges of the fovea in AMD eyes.
To summarize, the eye concentrates just three xanthophylls, dietary zeaxanthin, non-dietary meso-zeaxanthin and lutein in the macula (and other ocular tissues.) While there are 16-20 carotenoids in the blood serum, only two are selected for deposition and hyper-concentration in the eye. This highly selective process is the most specific distribution in the entire field of carotenoid biochemistry.
Non-Dietary or Meso-Zeaxanthin. This isomer is not found in the human diet or blood serum and is currently believed to be biotransformed from lutein. Levels of this isomer also have a specific spatial distribution. Why does this biotransformation take place only in the eye and nowhere else in nature?
There are currently three theories to explain this rare phenomenon:
a) Biological artifact
b) Reaction product of photooxidation
c) A highly specific ocular-tissue specific enzyme based reaction to transform the more prevalent xanthophyll, lutein, into a compromise structure closer to the structure of dietary zeaxanthin.
This specific biotransformation converts the bent structure of lutein by migration of a double bond. Thus, meso-zeaxanthin has a three-dimensional structure closer to the non-bent or straight structure, dietary zeaxanthin. The meso-zeaxanthin would again have 11 instead of 10 conjugated double bonds making its antioxidant strength closer to dietary zeaxanthin. This would mean the eye specifically works to create a compromise structure from the more abundant lutein (lutein is 5-10 times more abundant than dietary zeaxanthin in the blood and 10-20 times more prevalent in the diet.). This selective uptake of zeaxanthin over lutein has also recently been shown in the human brain. In this neura |