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Capsanthin, Zeaxanthin & Cryptoxanthin: The “Other” Carotenoids for Eye Health


If I asked you to name an important carotenoid for eye health, you’d likely say “lutein,” and you’d be right—but only partially. While lutein is certainly the most well know of the ocular carotenoids, there are others that play vital roles as well. These include capsanthin, zeaxanthin and cryptoxanthin. This article will focus on the value of these other carotenoids for eye health.

Before jumping into a discussion of these carotenoids, let’s first gain an understanding of the eye health issues they help address, and the relationship to digital devices.

Digital Device Exposure

Too much blue light exposure from digital devices can damage light-sensitive cells in the retina.1-4 So, how much blue light exposure does it take to result in eye damage, and what is the extent of that damage? Research indicates that headache, eye fatigue and other indications of eye strain are associated with the daily use of video display terminals on computers and other electronic devices and are common with three or more hours/day of exposure; and such exposure is common. In fact, 30 percent of adults spend more than half their waking hours (more than nine hours) using a digital device, 50 percent of Americans use digital devices more than five hours a day, and 70 percent use two or more digital devices at the same time.5 Furthermore, this digital light overexposure can contribute toward age-related macular degeneration and early-onset glaucoma.

Age-related Macular Degeneration

Age-related macular degeneration (AMD) is an eye disease that often occurs in older persons and affects the part of the eye called the macula that is especially important for seeing clearly. It can blur the sharp, central vision you need for activities like reading and driving, and generally make it harder to see faces or do close-up work like cooking or fixing things.6

Early-onset Glaucoma

Glaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in peripheral vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing and abnormal sensitivity to light (photophobia). The term “early-onset glaucoma” may be used when the disorder appears before the age of 40. In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.7 Zeaxanthin

Let’s begin the carotenoid discussion with a brief overview of zeaxanthin, which is relatively well-known and generally associated with lutein. The combination of these two carotenoids have considerable evidence suggesting important roles in eye health including protection against blue light.8-11 One of the main differences between them is how they are incorporated into cell (which means they absorb slightly different wavelengths of light). Lutein is more prominent at the edges of the retina and in the rods of the eye, while zeaxanthin is found primarily in the center of the retina. Also, zeaxanthin was found to adopt a roughly perpendicular orientation to the plane of the membrane, while lutein follows the perpendicular as well as parallel orientations. The effect on lipid membranes’ structural and dynamic properties seems to be a decrease in the lipid bilayer’s susceptibility to oxidative degradation—which is a good thing.12

Cryptoxanthin

β-Cryptoxanthin, a carotenoid found in fruits and vegetables such as tangerines, red peppers, and pumpkin, has several functions important for human health. It is an antioxidant and appears to be associated with decreased risk of some cancers and degenerative diseases.13 Other research has shown that plasma levels of β-cryptoxanthin were associated with a lower risk of advanced age-related macular degeneration.14 Being similar in structure to lutein and zeaxanthin, scientists have stated that further research on the role of β-cryptoxanthin on eye health would be useful.15

Capsanthin

Capsanthin is a carotenoid responsible for the red color of paprika. A major source of capsanthin is the pericarp of ripe red pepper (capsicum spp.). It has significant light absorbing properties and, among all other carotenoids, capsanthin is the most potent and has greater antioxidant activity. Even though capsanthin exhibits no provitamin A activity, it is regarded as functional nutrition due to its antioxidant and antitumor activities. Epidemiological studies indicate a protective role of capsanthin in colon carcinogenesis.16

The Combination of Capsanthin, Zeaxanthin And Cryptoxanthin

A capsanthin enriched fraction of Capsicum annum L fruits was developed, providing 50 percent to 80 percent capsanthin, 5 percent to 15 percent zeaxanthin, and 1 percent to 5 percent cryptoxanthin, as well as trace amounts of other carotenoids in a stable form (CapsiClear from Unibar Corp). Two studies were conducted on this carotenoid combination, one in rats, the other in humans.

The Study on Rats

In this study,17 Albino Wistar rats with experimental glaucoma were treated orally with the combination of capsanthin, zeaxanthin and cryptoxanthin (CapsiClear), and pilocarpine 2 percent eye drops were used as a standard drug. Intraocular pressure (IOP) levels were determined after oral administration of a low, medium and a high dose of the capsanthin enriched fraction (20, 40 and 80 mg/kg body weight). In rats with elevated IOP in both eyes, oral administration of capsanthin enriched fraction resulted in a significant reduction in IOP (p < .05) even at a low dose of 20 mg/kg body weight. There were no treatment-related changes in histopathology, hematology and clinical chemistry parameters. Consequently, when administered orally in IOP-bearing rats, capsanthin enriched fraction successfully reduced IOP without any adverse effects. The research concluded that capsanthin enriched fraction can be used to prevent permanent vision loss due to AMD and high intraocular pressure and can be useful in the treatment of glaucoma.

The Study on Human Subjects

A 12-week, placebo-controlled human clinical study18 was conducted at the University of North Texas to determine the effect of the combination of capsanthin, zeaxanthin and cryptoxanthin (as 40 mg/day CapsiClear) on biological and functional changes in a broad set of measures of eye/macular health. There were several meaningful results.

• Cumulative Macular Pigment Optical Density—Cumulative macular pigment optical density (MPOD), which reflects the protective capacity of the carotenoids against blue light damage, were increased at four weeks with the capsanthin enriched fraction (CapsiClear), with additional increases at eight and 12-weeks when compared to the placebo.

• Cumulative Photo Stress—Cumulative photo stress recovery is a measure of how long it takes for visual acuity to be restored after the retina is overloaded with a pen light (imitating the response from looking at the sun). A lower number in this case is better because a faster photo stress recovery signifies that the eye is able to readjust quickly to bright light, decreasing the risks that accompany temporary vision impairment, such as when driving a vehicle. The ability to recover from photo stress is directly related to MPOD. Also, just like MPOD, the capsanthin enriched fraction response was more effective than placebo.

• Cumulative Reading Under Blue and White Light—The ability to read under different cases of light exposure was tested. In this case a more negative number means a faster reading time. The subjects were given a random passage of words that was matched to their measured visual acuity and asked to read the words as quickly as possible. The test was conducted with one random passage under blue light and a second random passage under white light. In both cases the with the capsanthin enriched fraction outperformed the placebo. These are direct measures of reading performance under different light conditions.

Safety

A separate study was conducted to assess the safety of the capsanthin enriched fraction (CapsiClear). Single oral administration at levels of 2,000 mg/kg of body weight to two groups of three female Sprague Dawley rats each caused:

• No mortality in female rats, at 2,000 mg/kg b.wt.
• No abnormal clinical signs, at 2,000 mg/kg b.wt.
• No treatment related change in body weight was observed
• No abnormality detected at necropsy

Treatment with the capsanthin enriched fraction to Sprague Dawley rats at the dose level of 2,000 mg/kg body weight had no noteworthy effects on the general health of the animals nor the body weight and macroscopic lesions.

Conclusion

The capsanthin enriched fraction of Capsicum annum L fruits (CapsiClear from Unibar Corp) provides a combination of capsanthin, zeaxanthin and cryptoxanthin, shown in research to help reduce intraocular pressure in rats with glaucoma. Likewise, in human research this same carotenoid combination was demonstrated effectiveness in increasing MPOD that positively influenced photo stress recovery and blue light resistance. VR

References

1 Tosini G, Ferguson I, Tsubota K. Effects of blue light on the circadian system and eye physiology. Mol Vis. 2016 Jan 24;22:61-72.

2 Wu J, Seregard S, Algvere PV. Photochemical damage of the retina. Surv Ophthalmol. 2006 Sep-Oct;51(5):461-81.

3 Algvere PV, Marshall J, Seregard S. Age-related maculopathy and the impact of blue light hazard. Acta Ophthalmol Scand. 2006 Feb;84(1):4-15.

4 Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR). 2012. Health Effects of Artificial Light. Accessed from http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_035.pdf.

5 Richer S. Lutein and zeaxanthin protect against “bad blue” light. Eye Health Insider. December 2016: 4.

6 Age-related macular degeneration (AMD): Overview. InformedHealth.org

7 US National library of medicine. https://ghr.nlm.nih.gov/condition/early-onsetglaucoma.

8 Johnson EJ. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr Rev. 2014;72:605–612.

9 Aronow ME, Chew EY. Age-related Eye Disease Study 2: perspectives, recommendations, and unanswered questions. Curr Opin Ophthalmol. 2014;25:186–190.

10 Chew EY. Nutrition effects on ocular diseases in the aging eye. Invest Ophthalmol Vis Sci. 2013;54:ORSF42–ORSF47.

11 Koushan K, Rusovici R, Li W, et al. The role of lutein in eye-related disease. Nutrients. 2013;5:1823–1839.

12 Bernstein PS, LI B, Vachali PP, et al. Lutein, Zeaxanthin, and meso-Zeaxanthin: The Basic and Clinical Science Underlying Carotenoid-based Nutritional Interventions against Ocular Disease. Prog Retin Eye Res. 2016 Jan; 50: 34–66.

13 Burri BJ, La Frano MR, Zhu C. Absorption, metabolism, and functions of β-cryptoxanthin. Nutr Rev. 2016 Feb; 74(2): 69–82.

14 Wu J, Cho E, Willett WC, et al. Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up. JAMA Ophthalmol. 2015 Dec;133(12):1415-24.

15 Burri BJ, La Frano MR, Zhu C. Absorption, metabolism, and functions of β-cryptoxanthin. Nutr Rev. 2016 Feb; 74(2): 69–82.

16 Shanmugham V, Subban R. Extraction of capsanthin from Capsicum annum L fruits and its effect on carbomer- induced intraocular pressure in Albino Wistar rats. J Food Biochem. 2021;00:e13776.

17 Shanmugham V, Subban R. Extraction of capsanthin from Capsicum annum L fruits and its effect on carbomer- induced intraocular pressure in Albino Wistar rats. J Food Biochem. 2021;00:e13776.

18 Determining the Effect of 12-weeks of Oral Capsanthin Supplementation on Body Weight, Lipid Profile, Liver Health, and Eye/Macular Health in Overweight Subjects. Study conducted by Dr. Brian et al at University of North Texas and sponsored by Unibar Corporation, USA.

Gene Bruno, MS, MHS, the dean of academics for Huntington University of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at gbruno@hchs.edu.

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