The Macular Carotenoids Lutein and Zeaxanthin Are Related
to Increased Bone Density in Young Healthy Adults

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   Foods. 2017 (Sep 7);   6 (9). pii: E78 ~ FULL TEXT

Woodson K, Tangrea JA, Barrett MJ, Virtamo J, Taylor PR, Albanes D

Behavioral and Brain Sciences,
University of Georgia,
Athens, GA 30602, USA.
bhammond@uga.edu

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Lutein (L) and zeaxanthin (Z) status can be quantified by measuring their concentrations both in serum and, non-invasively, in retinal tissue. This has resulted in a unique ability to assess their role in a number of tissues ranging from cardiovascular to central nervous system tissue.

Recent reports using animal models have suggested yet another role, a developmental increase in bone mass. To test this, we assessed L and Z status in 63 young healthy adults. LZ status was determined by measuring LZ in serum (using HPLC) and retina tissue (measuring macular pigment optical density, MPOD, using customized heterochromatic flicker photometry). Bone density was measured using dual-energy X-ray absorptiometry (DXA).

Although serum LZ was generally not related to bone mass, MPOD was significantly related to bone density in the proximal femur and lumbar spine. In general, our results are consistent with carotenoids, specifically LZ, playing a role in optimal bone health.

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From the FULL TEXT Article:

Introduction

In a recent experimental study using growing mice as a model, Takeda et al. (2017) found that the dietary carotenoid, lutein (L), stimulated bone formation (increasing the density of, largely, cortical bone) by suppressing bone resorption. [1] A very similar result, also using young mice as a model, was reported by Tominari et al. (2017) who also found that L enhanced bone mineralization by suppressing osteoclastic bone resorption. [2] A direct study of the role of L on the bone health of humans, however, is limited to two studies. Wattanapenpaiboon et al. (2003) studied 205 subjects ranging from 26 to 86 years of age. [3] For premenopausal women, the higher areal bone mineral density (aBMD) of the lumbar spine was related to a greater dietary intake of L and zeaxanthin (Z) combined (N = 47, r = 0.35, p < 0.05). No effect, however, was found for men (N = 68; r = –0.18) or postmenopausal women (N = 90, r = 0.18). Sahni et al. (2009) did not find significant cross-sectional associations (N = 976) between the dietary intake of LZ and aBMD (at the femoral neck, trochanter, spine, and radial shaft) when only older subjects were assessed (mean age 75 years). [4] Despite the absence of an effect at the baseline, a higher intake of LZ for male subjects (N = 193) was associated with less reduction in trochanter BMD after four years (p = 0.008). Both Wattanapenpaiboon et al. and Sahni et al. concluded that LZ was positively associated with bone health (despite their mixed results and the acknowledgments that serum LZ may not adequately characterize long-term dietary intake).

If L and Z do offer protection against bone loss, as the results from the experimental animal data on young mice suggests, then it would be useful to understand the association between LZ status and bone health prior to the onset of the degeneration that is commonly seen in aging samples. Past research has included subjects in their 60s and 70s, whose bone health is likely to already reflect the consequences of oxidative stress.

To this end, we assessed a sample of younger subjects. LZ status was determined both by measuring fasting serum levels (a measure most likely reflecting acute intake) and retinal levels (a measure most likely reflecting longer term dietary strategies; [5, 6]). Bone density was determined by dual-energy X-ray absorptiometry (DXA) focusing on the proximal femur and lumbar spine

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Discussion

Our results indicate that individuals with a higher areal bone mineral density (aBMD) of the proximal femur and lumbar spine also tend to have higher MPOD. The relationship between serum LZ and skeletal mass, however, was not statistically significant. This may reflect the fact that macular pigment and bone density tend to reflect life-long habits, whereas serum LZ reflects a more short-term dietary intake. Recent experimental data are consistent with a specific role of lutein on promoting bone resorption and formation. This question of specificity is central. For example, if LZ status is simply a good marker for fruit and vegetable intake, then these correlations might simply be reflecting, e.g., other carotenoids. Other carotenoids have, in fact, been shown to promote bone health, such as lycopene [12], beta-cryptoxanthin [13], and beta-carotene [4]; although data regarding associations of these nutrients and skeletal mass are inconsistent. [14, 15] It is worth noting, however, that the relations we did find were to tissue levels of LZ and not serum. Unlike serum, macular pigment density does not tend to correlate with the dietary or serum levels of other carotenoids; even the relation to LZ in serum is fairly moderate (about r = 0.30 for this sample). Relationships between LZ status and calories expended and calcium/vitamin D intake are listed in Table 3. In general, these markers of health habits were not related to serum LZ status. Despite macular pigment not being highly related to other food components, it was associated with a greater caloric expenditure and higher self-reported intake of calcium and vitamin D. This moderate relationship was unexpected. Food sources for carotenoids (such as green leafy vegetables) tend to be very different than food sources for calcium (such as dairy products) or vitamin D (such as fortified cereals, dark meat and fish, or sources such as the sun). No evidence currently exists showing that calcium or vitamin D (more carefully measured than in this smaller study) are significant predictors of retinal L and Z levels. Large studies that have examined the relation between MPOD, physical activity, and sun exposure have, likewise, reported no relations. [16, 17] Our estimate of calcium and vitamin D intake was relatively rough and our sample size was relatively small (both factors reducing our ability to statistically control these variables). Nonetheless, given the moderate relations to MPOD, at least some level of confounding is possible and should be regarded as a limitation of this study.

In addition to effects on resorption and bone formation, if LZ is, in fact, related to a higher bone density later in life, it may be mediated by reducing oxidative stress that promotes bone loss (e.g., by helping to maintain a proper antioxidant/oxidant balance necessary for bone health [18]). A proper balance between osteoclast and osteoblast activity can be maintained with a proper balance between antioxidants and oxidants. [19] Excessive oxidative activity, however, also attenuates bone mass over time. [20] The production of reactive oxygen species (ROS) is a normal part of the bone remodeling process, which involves the coupling of osteoblasts and osteoclast functioning. Osteoclasts form and remove bone, resulting in the production of ROS, followed by an increase in bone formation by osteoblasts. However, if ROS production outweighs antioxidant mechanisms, subsequent increases in oxidative stress may result in accelerated bone loss. If LZ do promote bone health by lowering oxidative stress, then dietary intervention may not immediately impact bone density in young, healthy individuals who have most likely reached peak bone mass and not yet experienced significant bone loss. However, consistent with the young mouse models, dietary LZ could influence bone development in the very young. For example, do young infants with high LZ exposure have skeletal differences when compared to infants with minimal LZ exposure (e.g., infants given formula with no LZ added)? Another interesting group to study would be those reflecting not rapid development, but rapid decline (e.g., prespondylitic elderly women). Consistent with this, Sahni and colleagues (2009) were able to see an effect of LZ in the diet after following a sample of elderly subjects for four years, even though baseline associations between dietary LZ and bone density were not significant. [4] Subjects with greater LZ in their diet not only had reduced bone loss compared to other subjects, their bone density was actually higher than their baseline measurement.

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Conclusions

Our results indicate a significant relationship between bone mineral density and a biomarker of LZ status that reflects long-term habits. These cross-sectional data, coupled with recent experimental data in animal models [1, 2], fit well within the general conclusion [21] that maintaining a healthy diet over time can improve bone mineral status and may reduce the probability of clinical outcomes such as osteoporosis and fracture risk.

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