Lutein

I noticed a difference with astaxanthin as well.

Check this out:

http://www.gowell.co.th/en_article_detail.php?nid=4

Solid references

reaganry The only human study involves both Saw Palmento and astaxanthin. So who knows how much each compound contributes to the DHT lowering effect. Saw Palmento has been used for years to treat enlarged prostate because of knowledge of this effect.

The other study is in-vitro, not even in an animal, and doesn't mean much imo. I honestly take more faith in the couple of anecdotes than in the in-vitro.

More reason to be moderate with the dose though.

Gurm I take 4 mg because in one study 2 mg was found to reduce inflammation and 8 mg increased inflammation. This study was in humans (https://www.ncbi.nlm.nih.gov/pubmed/20205737). Also astaxanthin is highly lipid soluble and builds up in the eye tissues over time (weeks), just like lutein. You want the build up in the eye and not a ton of it floating around in your blood. Because of that I think a moderate dose over a long period of time is the best choice.

On the topic of the dose dependent effect (in the powerpoint) I think the measuring period is not long enough (28 days in that study) to fully gain the benefit of the lower dose, which will take a longer time to accumulate.

It's really easy to overdo any supplement that is lipid soluble and accumulates and eventually turns into toxicity. Think Vit D and A.

Gurm Donno about toxicity, but I wouldn't take more lutein without also taking more zeaxanthin as well. Zeaxanthin absorbs a slightly different band of blue light and I wouldn't want to crowd it out, although they do have a slightly different distribution in the eye as well.

There is also a debate over zeaxanthin vs meso-zeaxanthin. Not sure what to make of it. They may have different properties and most supplement manufactures label their meso-zeaxanthin as zeaxanthin.

Found a nice article on the different xanthophylls and the eye:

Lutein, Zeaxanthin, and meso-Zeaxanthin: The Basic and Clinical Science Underlying Carotenoid-based Nutritional Interventions against Ocular Disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698241/

I'll post some choice quotes and pictures with some commentary:

meso-zeaxanthin is found in the eye

believed to be formed at the macula by metabolic transformations of ingested carotenoids

Just in case you were wondering

monkey eyes are relatively easier to obtain soon after death compared to human eyes

The 3 xanthophylls discussed have varying distribution throughout the eye

Near the fovea there is twice as much zeaxanthin and meso-zeaxanthin as lutein; but, in the peripheral retina, this relationship is reversed, and zeaxanthin and meso-zeaxanthin levels are half as much as those of lutein... In the central retina, equal concentrations of lutein, zeaxanthin and meso-zeaxanthin are present; however, the ratio of meso-zeaxanthin to zeaxanthin decreases with the increased eccentricity to the fovea

A nice picture of that

Getting zeaxanthin and not meso-zeaxanthin in your supplement looks even more important, since meso-zeaxanthin probably naturally occurs in the eye after transformation from lutein

This conformational similarity of meso-zeaxanthin to lutein makes it more likely that lutein rather than zeaxanthin is the immediate precursor to meso-zeaxanthin... conversion of lutein to meso-zeaxanthin most likely takes place in the eye

This figure shows how xanthophylls neutralize ROS from blue light

There is something to be said about reducing unstable omega-6 polyunsaturated fats from your diet and replacing them with omega-3 and monounsaturated fats, which provide stability to cell membranes and with less potential for ROS generation

The potential for generation of ROS in the retina is high. The outer retina, especially membranes of the outer segments of the photoreceptors, has high concentrations of polyunsaturated fatty acids that are susceptible to photo-oxidation

Cool

With aging, the RPE gradually accumulates lipofuscin... There is solid experimental evidence that... a component of lipofuscin, can damage the RPE, is toxic to mitochondria, and induces apoptosis of cultured RPE cells when exposed to blue light... When RPE cells are treated with lutein, this phototoxic effect is reduced greatly... The presence of lutein and zeaxanthin has further been shown to reduce the amount of lipofuscin formed in cultured RPE cells and in vivo

Take it with a fatty meal

Given their hydrophobic nature, there is evidence that consuming carotenoid-rich foods in the presence of oils or cholesterol may increase their uptake

Some answers on the safety of a high lutein dose. 1 mg / kg of bodyweight

the European Food Safety Authority (EFSA) Panel on Food Additives and Nutrient Sources added to Food established an acceptable daily intake of 1 mg / kg bodyweight / day for lutein preparations derived from marigold

Although you could probably take much more if you wanted

The no observed-adverse-effect-level (NOAEL) for lutein/zeaxanthin concentrate was determined to be 400 mg/kg bodyweight/day

Absorption spectrum (MP is macular pigment)

The absorption maximum of lutein is 445 nm, while the maxima of zeaxanthin and meso-zeaxanthin are 450 nm... MP absorbed light between the wavelengths 430 nm and 490 nm, with maximum absorption taking place at ∼460 nm

HDL cholesterol transports xanthophylls to the eye. We love our HDL, folks.

The Wisconsin hypoalpha mutant (WHAM) chicken, a natural animal model of HDL deficiency, has a >90% reduction in plasma HDL.... When these chickens are fed a high-lutein diet, lutein levels increase in plasma, heart, and liver, but not in retina, suggesting that HDL is critical for delivery of carotenoids to retinal tissue

Article then goes on to identify some gene polymorphisms that could impair lutein and zeaxanthin binding in the eye and lead to problems.

Primates have very similar eyes to humans

RPE are retinal pigment cells, and light must pass through them to reach your photoreceptors.

Some more support for omega-3s (n-3 fatty acids)

In xanthophyll-free monkeys, they observed a dip in the RPE cell density profile at the foveal center. They also observed a difference in the RPE profile depending upon the level of n-3 fatty acids. Thus, they concluded xanthophylls and n-3 fatty acids are essential for the development and maintenance of RPE cells

Article then talks about rodent and avian models, but their eyes aren't similar enough.

Very nice

There is a growing and evidence-based consensus that MP is important for optimal visual performance because of its blue light-filtering properties and consequential attenuation of chromatic aberration, veiling luminance, and blue haze

A picture on the absorption spectrum of macular pigment (which is made up of lutein and zeaxanthin)

Continuing on that same article

We already know about AMD prevention, so lets look at its optical properties.

...Beyond its “protective” hypothesis, MP's optical and anatomic properties have prompted the “optical” hypotheses of this pigment... include MP's ability to enhance visual function and comfort by attenuation of the effects of chromatic aberration (Figure 12) and light scatter (Figure 13), via its light-filtering properties... MP could improve acuity by reducing the deleterious effects associated with the aberration of short-wave light

Wait a second though

However, in 2007 Engles et al modelled and evaluated the hypothesis and found that MPOD did not correlate significantly with either gap or hyperacuity measured in the yellow or white conditions, and therefore, their data did not support the predictions of the acuity hypothesis

Since a reduction in luminance isn't really harmful for us (frankly, I can't make my monitor any darker, and it still seems too bright), I'll take the reduction in luminance in exchange for a cleaner visual field with less aberrations

It appears that any acuity advantage gained by higher levels of MP is offset by a commensurate reduction in luminance (which correlates positively with acuity). It has also been suggested that MP could enhance the contrast of objects on a background via color filtering... This hypothesis was recently tested and found to be tenable, which has important implications for visual function in the non-diseased eye

Sounds good to me

For example, under natural conditions (e.g. walking outside), objects are often presented on short-wavelength backgrounds, such as a blue sky or green leaves, meaning that the filtering properties of MP is likely to impact positively on real-life vision. MP's pre-receptoral filtration of short-wavelength (blue) light is believed to reduce the adverse impact of glare disability, light scatter and chromatic aberration, thereby optimizing contrast sensitivity... It follows, therefore, that augmentation of MP would result in enhanced contrast sensitivity and improved glare disability

Here are their illustrations of chromatic aberration and light scatter

Next there is a diagram on the visual benefits of xanthophyll supplementation in healthy subjects. It's been studied since 1948 and most of trials found benefits in healthy people. However trial design has come a long way since then.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698241/table/T1/

Patience, young grasshoper

Of note, however, this modest augmentation in MP using a lutein-based formulation was observed only at the 12-month study visit

Next up, in this trial the group taking all 3 xanthophylls had the most improvement

Tthe second group was given 10 mg lutein, 10 mg meso-zeaxanthin and 2 mg zeaxanthin... every day for six months. A statistically significant increase in MP was observed (determined at three months following commencement of supplementation) only among subjects supplemented with a formulation containing all three macular carotenoids, including meso-zeaxanthin (Group 2). Statistically significant improvements in visual acuity were observed at six months, but only for subjects in Group 2

In conclusion, there is a biologically plausible rationale, supported by MP's light-filtering properties, which suggests that augmentation of MP will enhance visual function and comfort by attenuation of the effects of chromatic aberration and light scatter. Indeed, clinical trials have repeatedly shown that supplementation with the macular carotenoids lutein, zeaxanthin, and meso-zeaxanthin results in augmentation of MP, and consequential benefits in visual performance such as improved contrast sensitivity and reduced glare diability.

Next in the article is a bunch of stuff on AMD.

Good questions

The macula lutea contains lutein, zeaxanthin, and meso-zeaxanthin at a 1:1:1 ratio, yet the typical American consumes these carotenoids from the diet in a ratio of 5:1:0. AREDS2 teaches us that xanthophyll carotenoid supplementation has health benefits, but is the current 10 mg lutein and 2 mg zeaxanthin dose optimal? Would higher levels of supplementation and/or altered ratios of these three carotenoids increase MP more efficiently and promote better vision and lessen risk of AMD progression? Now that meso-zeaxanthin is readily available from commercial sources, is it beneficial to bypass the postulated ocular enzymatic metabolism of lutein to meso-zeaxanthin by supplying it pre-formed in a supplement? Are there any long-term consequences to consuming high concentrations of all three macular carotenoids, given that a typical diet contains circa 1.5 mg per day of lutein and zeaxanthin, and little or no meso-zeaxanthin? In light of our current knowledge that known binding proteins cannot discriminate between zeaxanthin and meso-zeaxanthin, should both be administered in equal amounts, or is one preferred over the other?

I also think in addition to lutein, zeaxanthin, and n-3, that anthocyanidins and proanthocyanidins (from blueberries, grade seed extract, or pine bark extract) could also be beneficial in the stressed eye. They have significantly less evidence than the other options, but I make sure to get a large serving of blueberries in a smoothie every morning. It can't hurt.

Confirmed sources of 3R 3R zeaxanthin (non meso) are any supplements specifying their zeaxanthin as ZeaGold or ZeaOne/OptiSharp. Doctor's Best has one. So does Eye Promise.