Vision 2020

B Vitamins Needed for Omega-3 Brain Benefits?

We asked an optometrist, ophthalmologists and nutrition scientists what they envision as key areas of focus for nutrition and ocular health in 2020 and beyond. Here are their predictions.

Stephen Pflugfelder, MD. Cullen Eye Institute, Baylor College of Medicine.
Prediction: We’ll learn more about how dietary components help protect the ocular surface.

There is ever increasing evidence that nutrition is an important factor for maintaining ocular health, including preventing macular degeneration and dry eye. While the exact mechanisms for these protective effects are still being investigated, I believe 2020 and beyond will bring greater insight into how these dietary components are working and how they contribute to a healthier ocular surface. 

It appears from research done by our group that dietary constituents, including vitamin A metabolites, DHA in fish oil, and vitamin D can decrease dry eye associated inflammation via signaling through the retinoid X receptor alpha (RXRa). Age and disease related disruptions in ligand metabolism, delivery or receptor expression may reduce the activity of these nutrition-associated pathways. 

Interestingly, oleic acid, the predominant fatty acid in olive oil is also an RXRa ligand and this could explain the clinical improvement seen in the olive oil placebo group in the DREAM study. 

Paul Bernstein, MD, PhD. Moran Eye Center, University of Utah School of Medicine.
Prediction: Prenatal supplements may routinely include lutein and zeaxanthin in the future.

Having worked in the field of ocular nutrition for over two decades, I am pleased that we now have excellent basic science understanding of many key nutrients for age-related macular degeneration (AMD) such as lutein, zeaxanthin, and omega-3 fatty acids, and large randomized clinical studies such as AREDS2 have made nutritional interventions against AMD standard-of-care in appropriate populations. What lies ahead for ocular nutrition in the upcoming years and decades?

While we have a good grasp on ocular nutrition in the senior years, my research group is now exploring the roles of carotenoids at the other end of the lifespan. The macular carotenoid pigment is present at birth, implying a fundamental importance in early life beyond protection against AMD that we do not fully understand yet. Perhaps the macular pigment is important for structural and functional development of the visual system. We have recently initiated a two-year clinical study funded by the National Eye Institute on lutein and zeaxanthin in pregnancy (the L-ZIP study).

Sixty women in their first trimester of pregnancy will be randomized to standard-of-care prenatal vitamins with and without 10 mg of lutein and 2 mg of zeaxanthin. Our main outcomes will be maternal and infant carotenoid status in the eye, skin and plasma at birth along with structural assessment of infant foveal maturity. Going forward, we hope to continue to follow these children as they grow and mature to see if early nutritional intervention with carotenoids enhances visual and/or cognitive performance. If we see positive results, I foresee widespread incorporation of lutein and zeaxanthin in prenatal supplements around the world.

Kelly Nichols, OD, MPH, PhD. Dean, School of Optometry, University of Alabama at Birmingham.
Prediction: The field of nutrition science has garnered a lot of accolades and news commentary in the last year, and I don’t expect that to change in 2020 and beyond.

What we eat is now only part of the equation; how often and when we eat have become the topic of magazines, internet and more importantly science. Recent research conducted by Assistant Professor Courtney Peterson, PhD, Assistant Professor in the Department of Nutrition Sciences and a scientist in UAB’s Nutrition Obesity Research Center (NORC), Diabetes Research Center (DRC), and the UAB Comprehensive Diabetes Center (UCDC), has shown that intermittent fasting, or limiting the hours when eating occurs, improves blood sugar control, blood pressure, inflammatory events, and oxidative stress, even when people don't change eating habits. Her work has yet to cross over to the eyecare arena, but her focus on diabetes, lifestyle intervention, caloric restriction and intermittent fasting have made her work a “must watch” and are not far removed from all of the important elements we are interested in related to macular and overall ocular health.

My clinical research interest is in the area of ocular surface disease, and it is understood that dry eye and contact lens discomfort involve inflammation. I am convinced that low-to-moderate grade systemic inflammation plays a significant role in maintaining the homeostasis of the tear film and ocular surface. Future understanding of the role of intermittent fasting on systemic inflammation will be knowledge that crosses over many fields of science.

Allen Taylor, PhD. Director, Laboratory for Nutrition and Vision Research, Tufts University
Prediction: Greater understanding about the relationship of unhealthy carbohydrates, other dietary components, the microbiome and AMD risk. I predict that consuming lower glycemia diets will be the recommended standard of care for AMD patients.

Clearly, it would be a tremendous boon to personal and public health if risk for age related AMD could be limited by dietary management. Our group has focused on understanding how AMD is connected to the quality of carbohydrates one consumes.

Using baseline AREDS data, we found that diets with higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood (aka “Oriental” diet) were protective against early and advanced AMD, relative to the “Western” pattern of higher red and processed meat, high-fat dairy, French fries, refined grains, and eggs. Importantly, we found that the more one adhered to the Western pattern, the greater the risk for early or advanced AMD. Similarly, the more one subscribed to the Oriental food pattern, the less the risk for early or later AMD.

Epidemiologic studies indicate that consuming lower glycemic index (GI) diets is protective against risk for and progress of AMD. Lower GI diets are those low in carbohydrates that cause a rapid rise in blood glucose, such as white bread and rice, sugars, and processed foods with no to low fiber. Importantly, the benefits gained by consuming low GI diets are in addition to the benefits of eating Oriental or “prudent” diets.

To corroborate the apparent benefit of consuming lower GI diets to diminish risk for AMD, we fed two types of mice (Wild type, and Nrf2-/- with a compromised ability to mount stress and oxidant responses) either low or high GI isocaloric diets beginning at 12 months of age (middle-age) through 24 months of age (old age). After 6 months, half of the mice receiving the high GI diet were switched to the low GI diet. Mice fed the high GI diet displayed many features of AMD, including retinal pigment epithelial hyper-pigmentation and atrophy, lipofuscin accumulation, and photoreceptor cell loss. Those in the low-GI diet group did not. The low GI diet also limited advanced glycation end products (AGEs) and peroxidized lipids. Crucially, the damage seen while on the high GI diets was halted or reversed when mature mice were switched from the high to the low GI diet.

The diets also affected the microbiome and the blood and urinary metabolome, all of which were related to retinal integrity and to each other. In the WT mice, for example, the microbiomes were dramatically altered due to diet and age. Changing from high to low GI diet returned the micro-biome from the high GI profile to that of the older low GI diet animal.

The results suggest that switching to a low GI diet, even late in life, is beneficial. This is remarkable because it’s achievable without major behavioral changes. Our findings of many altered proteins, particularly AGEs, also indicate that glycation is altering bulk proteins as well as the enzymes that might normally selectively recognize and remove them. Additionally, we identified new, potential biomarkers for AMD – important because none are currently available. These will allow us to design new drugs and predict when people will get AMD and when to exploit diets or new drugs to diminish the AMD burden.

Lisa Olmos de Koo, MD, MBA. Ophthalmology Dept., University of Washington
Prediction: We may find that some botanical extracts can help mitigate the damaging effects of macular disease. 

There are several promising botanical extracts to watch for their use in macular disease. As we know, even those patients with early macular disease whose objective Snellen visual acuity is not affected often report subjective visual disturbances such as eye strain and poor contrast and flicker sensitivity, and it is exciting that supplementation with botanicals could possibly mitigate these effects, producing a better quality of vision for our patients. 
 
Saffron (Crocus sativus) is a spice with a history of traditional use as an herbal medicine for a variety of conditions throughout Eurasia and Africa. The spice comes from the flower stigma, which contains crocin and crocetin, carotenoids that have been shown in animals to protect photoreceptor morphology and function and protect against cellular death. The most recent and largest human study to date on saffron included 96 subjects with mild to moderate AMD and was double-blind, randomized, and placebo controlled. After 3 months of supplementation with 20 mg of saffron extract, mean-pooled multifocal ERG latency was reduced in the saffron group vs. placebo, along with a modest (< 1 letter) but statistically significant gain in visual acuity. Other smaller studies by a group of Italian researchers demonstrated improvement in focal ERG sensitivity in participants taking saffron for a longer period of time. We await the results of larger and longer future trials. 
 
Curcumin, a component of the spice turmeric, is another botanical extract of great interest. Turmeric is derived from the rhizome or root of Curcuma longa and is one of the main components of curry powder. In India and other parts of Asia, turmeric is used in traditional medicine to treat many health conditions. Pre-clinical and animal studies on curcumin have shown a protective effect on retinal pigment epithelial cells against oxidative stress. Low solubility and oral bioavailability have posed a challenge in the use of curcumin supplementation; however, recent small clinical trials on the effectiveness of curcumin formulated with a hydrophilic carrier in treating diabetic retinopathy have shown promising results.  

Penelope Edwards, MPH, CNS. SBH Nutrition Scientist
Prediction: Nutrition education will become an integral component of medical curricula.

As a UCLA grad student in nutrition in the 1970’s, I participated in the ½ day seminars in nutrition fundamentals that our division provided to medical students annually. The seminars, though woefully brief, seemed to be well received. Much has evolved in the field of nutrition since then, with evidence overwhelmingly showing that diet is vital to good health, including ocular health. An 18 year-long study published this month, for example, found that those eating an unhealthy “Western” diet had a three-fold greater risk of developing late AMD.

Unfortunately, not much has changed over the years in terms of incorporating nutrition into medical education, even though many Americans cite medical doctors as their most reliable source of information on diet and dietary supplements. The Harvard Law School Food Law and Policy Clinic reported last year that the average medical student spent less than 1% of lecture hours on nutrition, even as they note that nutrition training improves outcomes for patients and mitigates the immense costs of preventable diseases.

But that educational lag may be about to change. A pilot program at Wayne State University School of Medicine teaching 1st year med students the science behind plant-based nutrition – and how to integrate that knowledge into clinical practice – is enjoying early success, with plans to expand nationally. I predict that programs like this will catch on in the medical community in the foreseeable future, closing the gap in nutrition science education within the medical curriculum and ultimately improving patients' health.