EYESIGHT

[nicholson]

AMD is one of the major causes of (effective) blindness with age.  Someone I know has a moderately advanced case of it and is finding it a serious problem.  So today I googled the definition of 'drusen'.  Drusen are associated with AMD but likely are not the cause of it.  If you have lots of drusen it is likely you will soon start to see evidence of early stage AMD.  At my most recent very comprehensive eye examination I was told I have the very earliest signs of AMD, but:  "everyone your age has that."

 

Drusen are deposits that appear in the eye behind the retina with age.  It turns out that they are composed of fat.  So I searched using the expression:  'dietary fat age-related macular degeneration' ['dietary fat AMD' did not work].  And it turns out that, yes, high dietary total fat is associated with increased risk of AMD.  ***Linolenic acid*** in particular seems to be implicated, while DHA and fish appear to be somewhat beneficial.  Anyway, here is the abstract of the paper finding these associations:

=====================================

Am J Clin Nutr. 2001 Feb;73(2):209-18.

Prospective study of dietary fat and the risk of age-related macular degeneration.

Cho E¹, Hung S, Willett WC, Spiegelman D, Rimm EB, Seddon JM, Colditz GA, Hankinson SE.

Author information

Abstract

BACKGROUND:

The relation between intakes of total fat and specific types of fat and age-related macular degeneration (AMD) remains unclear.

OBJECTIVE:

Our objective was to examine prospectively the association between fat intake and AMD.

DESIGN:

We conducted a prospective follow-up study of participants in the Nurses' Health Study and the Health Professionals Follow-up Study. At baseline (1984 for women and 1986 for men), the study included 42743 women and 29746 men aged > or = 50 y with no diagnosis of AMD who were followed until 1996. Fat intake was assessed with a food-frequency questionnaire.

RESULTS:

We accrued 567 patients with AMD with a visual loss of 20/30 or worse. The pooled multivariate relative risk (RR) for the highest compared with the lowest quintile of total fat intake was 1.54 (95% CI: 1.17, 2.01; P for trend = 0.008). Linolenic acid was positively associated with risk of AMD (top versus bottom quintile of RR: 1.49; 95% CI: 1.15, 1.94; P for trend = 0.0009). Docosahexaenoic acid had a modest inverse relation with AMD (top versus bottom quintile of RR: 0.70; 95% CI: 0.52, 0.93; P for trend = 0.05), and >4 servings of fish/wk was associated with a 35% lower risk of AMD compared with < or = 3 servings/mo (RR: 0.65; 95% CI: 0.46, 0.91; P for trend = 0.009).

CONCLUSIONS: Total fat intake was positively associated with risk of AMD, which may have been due to intakes of individual fatty acids, such as linolenic acid, rather than to total fat intakes per se. A high intake of fish may reduce the risk of AMD.

PMID:  11157315

===================================  

If we are all gonna live to be at least 110 it would be nice to still be able to read when we get there.

 

Rodney.

 

[Dean Pomerleau]

Thanks Rodney,

 

My 23andMe results show my lifetime risk of developing AMD is about 5x the average person's risk (31% vs. 6.5%). For the last couple eye exams, I've been tracking the thickness of my macular and its relatively thin and getting (slightly) thinner. No drusen so far, thankfully. My opthamologist suggested I might want to start on the latest ARENDS-II formula of supplements, which includes:

 

• 10 mg lutein and 2 mg zeaxanthin
• 350 mg DHA and 650 mg EPA
• 25 mg zinc

The results of the results of the original ARENDS study [1] which supplemented with beta-carotene instead of lutein/zeaxanthin, vitamin C, E, more zinc and no DHA/EPA, was about a 25-30% reduction in progression of AMD, but also an increase in lung cancer (mostly in smokers), likely a results of the beta-carotene. In the follow-up ARENDS-II study [2] using the above formulation, they got basically the same results, but without the increase in lung cancer. So that's the formulation doctor's are recommending now for people with early stage AMD these days.

 

I already take zinc and some DHA/EPA (less that that though...), so a couple months ago I added lutein/zeaxanthin to my supplement regime in the 10/2 mg recommended dosage.

 

Coincidently, Al Pater sent out a paper [3] today from the Health Professionals / Nurses Health Study which confirmed the benefits of high (dietary) intake of lutein/zeaxanthin for preventing advanced AMD. The researchers in [3] found:

 

Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend < .001). Predicted plasma carotenoid scores for other carotenoids, including ß-cryptoxanthin, Alpha-carotene, and ß-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend < .001). 

 

So it seems like lutein/zeaxanthin can indeed be helpful for avoiding at least the progression of AMD.

 

If we are all gonna live to be at least 110 it would be nice to still be able to read when we get there.

 

I couldn't agree more!

 

--Dean

 

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[1] Opthalmology. 2013 Aug;120(8):1604-11.e4. doi: 10.1016/j.ophtha.2013.01.021.

Epub 2013 Apr 10.

Long-term effects of vitamins C and E, β-carotene, and zinc on age-related
macular degeneration: AREDS report no. 35.

Chew EY(1), Clemons TE, Agrón E, Sperduto RD, Sangiovanni JP, Kurinij N, Davis
MD; Age-Related Eye Disease Study Research Group.


OBJECTIVE: To describe the long-term effects (10 years) of the Age-Related Eye
Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement
on progression of age-related macular degeneration (AMD).
DESIGN: Multicenter, randomized, controlled, clinical trial followed by an
epidemiologic follow-up study.
PARTICIPANTS: We enrolled 4757 participants with varying severity of AMD in the
clinical trial; 3549 surviving participants consented to the follow-up study.
METHODS: Participants were randomly assigned to antioxidants C, E, and β-carotene
and/or zinc versus placebo during the clinical trial. For participants with
intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the
progression to advanced AMD. Participants were then enrolled in a follow-up
study. Eye examinations were conducted with annual fundus photographs and
best-corrected visual acuity assessments. Medical histories and mortality were
obtained for safety monitoring. Repeated measures logistic regression was used in
the primary analyses.
MAIN OUTCOME MEASURES: Photographic assessment of progression to, or history of
treatment for, advanced AMD (neovascular [NV] or central geographic atrophy
[CGA]), and moderate visual acuity loss from baseline (≥15 letters).
RESULTS: Comparison of the participants originally assigned to placebo in AREDS
categories 3 and 4 at baseline with those originally assigned to AREDS
formulation at 10 years demonstrated a significant (P<0.001) odds reduction in
the risk of developing advanced AMD or the development of NV AMD (odds ratio
[OR], 0.66, 95% confidence interval [CI], 0.53-0.83 and OR, 0.60; 95% CI, 0.47-0.
78, respectively). No significant reduction (P = 0.93) was seen for the CGA (OR,
1.02; 95% CI, 0.71-1.45). A significant reduction (P = 0.002) for the development
of moderate vision loss was seen (OR 0.71; 95% CI, 0.57-0.88). No adverse effects
were associated with the AREDS formulation. Mortality was reduced in participants
assigned to zinc, especially death from circulatory diseases.
CONCLUSIONS: Five years after the clinical trial ended, the beneficial effects of
the AREDS formulation persisted for development of NV AMD but not for CGA. These
results are consistent with the original recommendations that persons with
intermediate or advanced AMD in 1 eye should consider taking the AREDS
formulation.

PMID: 23582353

 

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[2] JAMA. 2013 May 15;309(19):2005-15. doi: 10.1001/jama.2013.4997.

Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration:
the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial.

Age-Related Eye Disease Study 2 Research Group.

Collaborators: Chew EY, Clemons TE, SanGiovanni JP, Danis R, Ferris FL 3rd, Elman
M, Antoszyk A, Ruby A, Orth D, Bressler S, Fish G, Hubbard B, Klein M, Chandra S,
Blodi B, Domalpally A, Friberg T, Wong W, Rosenfeld P, Agron E, Toth C, Bernstein
P, Sperduto R.

Erratum in
JAMA. 2013 Jul 10;310(2):208.

IMPORTANCE: Oral supplementation with the Age-Related Eye Disease Study (AREDS)
formulation (antioxidant vitamins C and E, beta carotene, and zinc) has been
shown to reduce the risk of progression to advanced age-related macular
degeneration (AMD). Observational data suggest that increased dietary intake of
lutein + zeaxanthin (carotenoids), omega-3 long-chain polyunsaturated fatty acids
(docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]), or both might further
reduce this risk.
OBJECTIVES: To determine whether adding lutein + zeaxanthin, DHA + EPA, or both
to the AREDS formulation decreases the risk of developing advanced AMD and to
evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in
the AREDS formulation.
DESIGN, SETTING, AND PARTICIPANTS: The Age-Related Eye Disease Study 2 (AREDS2),
a multicenter, randomized, double-masked, placebo-controlled phase 3 study with a
2 × 2 factorial design, conducted in 2006-2012 and enrolling 4203 participants
aged 50 to 85 years at risk for progression to advanced AMD with bilateral large
drusen or large drusen in 1 eye and advanced AMD in the fellow eye.
INTERVENTIONS: Participants were randomized to receive lutein (10 mg) +
zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), lutein + zeaxanthin and DHA +
EPA, or placebo. All participants were also asked to take the original AREDS
formulation or accept a secondary randomization to 4 variations of the AREDS
formulation, including elimination of beta carotene, lowering of zinc dose, or
both.
MAIN OUTCOMES AND MEASURES: Development of advanced AMD. The unit of analyses
used was by eye.
RESULTS: Median follow-up was 5 years, with 1940 study eyes (1608 participants)
progressing to advanced AMD. Kaplan-Meier probabilities of progression to
advanced AMD by 5 years were 31% (493 eyes [406 participants]) for placebo, 29%
(468 eyes [399 participants]) for lutein + zeaxanthin, 31% (507 eyes [416
participants]) for DHA + EPA, and 30% (472 eyes [387 participants]) for lutein +
zeaxanthin and DHA + EPA. Comparison with placebo in the primary analyses
demonstrated no statistically significant reduction in progression to advanced
AMD (hazard ratio

---

, 0.90 [98.7% CI, 0.76-1.07]; P = .12 for lutein +
zeaxanthin; 0.97 [98.7% CI, 0.82-1.16]; P = .70 for DHA + EPA; 0.89 [98.7% CI,
0.75-1.06]; P = .10 for lutein + zeaxanthin and DHA + EPA). There was no apparent
effect of beta carotene elimination or lower-dose zinc on progression to advanced
AMD. More lung cancers were noted in the beta carotene vs no beta carotene group
(23 [2.0%] vs 11 [0.9%], nominal P = .04), mostly in former smokers.
CONCLUSIONS AND RELEVANCE: Addition of lutein + zeaxanthin, DHA + EPA, or both to
the AREDS formulation in primary analyses did not further reduce risk of
progression to advanced AMD. However, because of potential increased incidence of
lung cancer in former smokers, lutein + zeaxanthin could be an appropriate
carotenoid substitute in the AREDS formulation.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.

PMID: 23644932

 

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[3] Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up.

Wu J, Cho E, Willett WC, Sastry SM, Schaumberg DA.
JAMA Ophthalmol. 2015 Oct 8:1-10. doi: 10.1001/jamaophthalmol.2015.3590. [Epub ahead of print]
PMID: 26447482
http://archopht.jamanetwork.com/article.aspx?articleid=2448581

Abstract

IMPORTANCE:

Despite strong biological plausibility, evidence from epidemiologic studies and clinical trials on the relations between intakes of lutein and zeaxanthin and age-related macular degeneration (AMD) has been inconsistent. The roles of other carotenoids are less thoroughly investigated.

OBJECTIVE:

To investigate the associations between intakes of carotenoids and AMD.

DESIGN, SETTING, AND PARTICIPANTS:

Prospective cohort study, with cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study in the United States. A total of 63,443 women and 38,603 men were followed up, from 1984 until May 31, 2010, in the Nurses' Health Study and from 1986 until January 31, 2010, in the Health Professionals Follow-up Study. All participants were aged 50 years or older and were free of diagnosed AMD, diabetes mellitus, cardiovascular disease, and cancer at baseline.

MAIN OUTCOMES AND MEASURES:

Predicted plasma carotenoid scores were computed directly from food intake, assessed by repeated food frequency questionnaires at baseline and follow-up, using validated regression models to account for bioavailability and reporting validity of different foods, and associations between predicted plasma carotenoid scores and AMD were determined.

RESULTS:

We confirmed 1361 incident intermediate and 1118 advanced AMD cases (primarily neovascular AMD) with a visual acuity of 20/30 or worse by medical record review. Comparing extreme quintiles of predicted plasma lutein/zeaxanthin score, we found a risk reduction for advanced AMD of about 40% in both women and men (pooled relative risk comparing extreme quintiles = 0.59; 95% CI, 0.48-0.73; P for trend < .001). Predicted plasma carotenoid scores for other carotenoids, including ß-cryptoxanthin, Alpha-carotene, and ß-carotene, were associated with a 25% to 35% lower risk of advanced AMD when comparing extreme quintiles. The relative risk comparing extreme quintiles for the predicted plasma total carotenoid index was 0.65 (95% CI, 0.53-0.80; P for trend < .001). We did not identify any associations of carotenoids, either as predicted plasma score or calculated intake, with intermediate AMD.

CONCLUSIONS AND RELEVANCE:

Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD.

[nicholson]

Thanks Dean.

 

Incidentally, I capitalized the subject line for this new thread in the hope that when/if others post about eyesight they may choose to do so in the same thread.  That way if, down the road, anyone wishes to read everything posted here on eyesight they can easily do so in just one place.

 

Rodney.

[BrianMDelaney]

And it turns out that, yes, high dietary total fat is associated with increased risk of AMD.  ***Linolenic acid*** in particular seems to be implicated, while DHA and fish appear to be somewhat beneficial.

 

Important topic -- thanks!

 

Rodney, the paper you cite is a bit tentative on linolenic acid:

 

"Polyunsaturated fat intake may promote oxidative damage by increasing the degree of unsaturation in the macula, a region particularly susceptible to oxidation due to light exposure and high oxygen tension (24). However, linolenic acid is a minor fatty acid in the macula (7). The lack of a specific biologic mechanism for linolenic acid and the fact that we assessed many individual fatty acids, and thus, [the fact that] this could be a chance finding, emphasizes the need for further assessments of these associations." (My emphasis.)

 

I'd like to see follow-up work done before we start worrying about linolenic acid. I suspect it's an innocent bystander in some other causal relation (although the researchers did rule out many potential non-bystanders).

 

- Brian

[BrianMDelaney]

 

Coincidently, Al Pater sent out a paper [3] today from the Health Professionals / Nurses Health Study which confirmed the benefits of high (dietary) intake of lutein/zeaxanthin for preventing advanced AMD.

 

[...]

 

So it seems like lutein/zeaxanthin can indeed be helpful for avoiding at least the progression of AMD.

 

-------------

[3] http://archopht.jamanetwork.com/article.aspx?articleid=2448581

 

[...]

Higher intake of bioavailable lutein/zeaxanthin is associated with a long-term reduced risk of advanced AMD. Given that some other carotenoids are also associated with a lower risk, a public health strategy aimed at increasing dietary consumption of a wide variety of fruits and vegetables rich in carotenoids may reduce the incidence of advanced AMD. [My emphasis.]

 

Not sure about your "So it seems". Could be the case, and it's consistent with the findings, but a cursory glance at the study makes me think we really can't rule out some other effect: maybe it's all the carotenoids and even other phytochemicals put together that reduce risk.

 

CRON-O-Meter shows me at 7-9 mg of "Lutein+Zeaxanthin" most days, plus oodles of other carotenoids, and my assumption has been that adding supplemental lutein and zeaxanthin to that probably won't give me additional protection. But I admit haven't looked into the research carefully.

 

- Brian

[Dean Pomerleau]

All,

 

Here is a popular report of a cool new study [1] on preventing AMD with L-Dopa the drug used to treat Parkinson's Disease.

 

There are two things that are noteworthy about this study. First, L-Dopa appears pretty effective at preventing macular degeneration (~20% risk reduction), and as impressive, appeared to delay onset of AMD by about 8 years on average. So here is another hope for those of us who are at elevated risk for AMD.

 

The other cool thing about this study is that the results were discovered purely through data mining. They call it a "virtual prospective" study. They looked at the medical records of something like 10 million people and identified those relatively few (~20,000) who took L-Dopa (for Parkinson's disease) and a similar number of other people with Parkinson's disease but who didn't take L-Dopa. They made sure all the selected subjects had ophthalmology data both before any of them had AMD and many years later.

 

So they basically used "big data" mining to discover, or at least validate a hypothesis about, a new potential preventative measure for AMD. Obviously people with Parkinson's disease are a special group, so the finding will have to be validated with a general population.

 

But both the treatment, and the study methodology are extremely interesting.

 

--Dean

 

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[1] Mining Retrospective Data for Virtual Prospective Drug Repurposing: L-DOPA and Age-related Macular Degeneration

 

Murray H. Brilliant, Ph.D., Kamyar Vaziri, MD., Thomas B. Connor Jr. Jr., MD, Stephen G. Schwartz, MD, MBA, Joseph J. Carroll, Ph.D., Catherine A. McCarty, Ph.D., MPH., Steven J. Schrodi, Ph.D., Scott J. Hebbring, Ph.D., Krishna S. Kishor, MD., Harry W. Flynn Jr. Jr., MD., Andrew A. Moshfeghi, MD., Darius M. Moshfeghi, MD., M Elizabeth Fini, Ph.D., Brian S. McKay, Ph.D.correspondenceemail

Published Online: October 30, 2015

Open Access|Article has an altmetric score of 125

DOI: http://dx.doi.org/10.1016/j.amjmed.2015.10.015

Full Text: http://www.amjmed.com/article/S0002-9343%2815%2901019-0/abstract

 

Background

 

Age-related Macular Degeneration (AMD) is a leading cause of visual loss among the elderly. A key cell-type involved in AMD, the retinal pigment epithelium expresses a g-protein coupled receptor that, in response to its ligand, L-DOPA, upregulates pigment epithelia derived factor, while downregulating vascular endothelial growth factor. In this study we investigated the potential relationship between L-DOPA and AMD.

 

Methods

 

We used retrospective analysis to compare the incidence of AMD between patients taking vs. not taking L-DOPA. We analyzed 2 separate cohorts of patients with extensive medical records from the Marshfield Clinic (∼17,000 and ∼20,000) and the Truven MarketScan outpatient and databases (∼87 million) patients. We used ICD-9 codes to identify AMD diagnoses and L-DOPA prescriptions to determine the relative risk of developing AMD and age of onset with or without an L-DOPA prescription.

 

Results

 

In the retrospective analysis of patients without an L-DOPA prescription, AMD age of onset was 71.2, 71.3 and 71.3 in three independent retrospective cohorts. AMD occurred significantly later in patients with an L-DOPA prescription, 79.4 in all cohorts. The odds ratio of developing AMD was also significantly negatively correlated by L-DOPA (OR=0.78;CI=0.76-0.80;P<0.001). Similar results were observed for neovascular AMD, p<0.001.

 

Conclusion

 

Exogenous L-DOPA was protective against AMD. L-DOPA is normally produced in pigmented tissues such as the retinal pigment epithelium as a byproduct of melanin synthesis by tyrosinase. GPR143 is the only known L-DOPA receptor, it is therefore plausible that GPR143 may be a fruitful target to combat this devastating disease.

 

Research Highlights

 

•Retrospective clinical study to test whether L-DOPA may protect from AMD.

•Patients taking L-DOPA have reduced risk of developing AMD.

•L-DOPA delays the onset of AMD

•L-DOPA may be repurposed to prevent and delay AMD

[Ron Put]

I have been noticing that my lutein intake is pretty low, according to Chronometer.  I eat spinach maybe once or twice a week at best, but maybe should amp up my consumption of it.  For what it's worth, I am close to 60, never had to wear glasses even though I read and stare at a screen for much of the day, and apparently have high levels of linoleic acid, according to my recent blood panel. The eye exam I had last year cleared me of any evidence of AMD (he specifically noted that).

I am thinking of supplementing, even though the evidence appears unclear.  Anyone here who has come across any adverse effects associated with supplementation?

[TomBAvoider]

Ron, please note: the study cites linolenic acid not linoleic acid.

[corybroo]

According to wikipedia, there are two forms fo linolenic acid - do they have different effects?

 Linolenate (in the form of triglyceride esters of linolenic acid) is often found in vegetable oils; traditionally, such fatty acylates are reported as the fatty acids:

• α-Linolenic acid, an omega-3 (n-3) fatty acid
• γ-Linolenic acid, an omega-6 (n-6) fatty acid

[Ron Put]

On 8/16/2020 at 8:50 PM, TomBAvoider said:

linolenic acid not linoleic acid

Yep, I didn't read carefully enough.  Thanks for pointing it out.

But the question about supplementing with lutein and any potential adverse effects from long-term supplementation still remains.