What Supplements Are Useful in Diabetic Retinopathy?


The prevalence of diabetes in the United Kingdom (UK) has been rising, from 1.4 million people in 1996 to 3.5 million in 2019. The actual number of individuals living with diabetes in the UK is likely to be closer to 4 million, since many are undiagnosed. If nothing changes, this number is projected to rise to 5 million by 2025. Those numbers are only reflective of a single country. The worldwide estimate for diabetes prevalence is 416 million; that’s 1 in 11 people. Almost half of these people are not diagnosed. By 2040, the number of people living with diabetes worldwide is estimated to be 642 million.1

Along with diabetes comes the risk of retinopathy. Risk increases with duration of disease, worse metabolic control, elevated blood pressure and type 1 versus type 2 diabetes. Diabetic retinopathy can have devastating consequences to vision and remains a significant contributor to blindness. Worldwide, as of 2010, diabetic retinopathy accounted for 0.8 million of 32.4 million blind people. Of the 191 million people worldwide living with moderate to severe vision impairment, 3.7 million have diabetic retinopathy.2

Once diagnosed with diabetes, some causes of diabetic retinopathy are not controllable; these include the duration of disease or having type 1 versus type 2 diabetes. Other factors, like glycaemic control, are certainly manageable. In addition to diet and exercise, many patients turn to supplements for additional help. Vitamins, minerals and nutraceuticals can be a simple, cost-effective and safe way to address the underlying pathophysiology of ocular vascular disorders such as diabetic retinopathy. Supplementation with lutein, zeaxanthin, vitamin C, vitamin D, vitamin E, zinc, copper, alpha-lipoic acid, n-acetylcysteine, and complexes of B-1, B-2, B-6, L-methyl folate, and methyl B-12 have all been shown to be useful in diabetic retinopathy. These nutrients help to address the hyperhomocysteinaemia and neurotrophic factor depletion that results from vitamin deficiencies, antioxidant deficiencies and genetic mutations like Methylenetetrahydrofolate Reductase (MTHFR).3

Anthocyanosides, also known as anthocyanins, are a type of flavonoid that has been studied in the use of diabetic retinopathy for decades. There are hundreds of different anthocyanins, only twenty of which occur naturally. These can be found in many colourful fruits and vegetables, such as blueberries, raspberries, black rice and soybeans. One of the most potent sources of anthocyanins is Vaccinium myrtillus L., commonly known as bilberry. Bilberry contains cyanidin, delphinidin, malvidin, peonidin, and petunidin.4 Anthocyanins address a hallmark of diabetic retinopathy: vascular permeability. They have been shown to stabilise the cell membrane phospholipids by inhibiting peroxidation. They also stimulate the synthesis of glycosaminoglycans in connective tissue. There is also evidence that they reduce in platelet aggregation and increase erythrocyte flexibility, aiding in the prevention of haemorrhaging.5 By decreasing vascular permeability, anthocyanins have been found to be useful in retinopathies of hypertensive or diabetic origin.

bilberries in heart shaped bowl

In a double-blind, placebo-controlled trial, 40 people with either diabetic (87%) or hypertensive (13%) retinopathy were randomized to one of two treatment groups. Half received a placebo, while the other half received one 160 mg capsule of Vaccinium myrtillus L. anthocyanins twice daily. Patients underwent ophthalmoscopic examination at baseline, and again after 30 and 60 days. 77% of the treatment group showed improvement in their retinopathy, while none of the placebo group did. After the crossover, 80% of the treatment group showed improvement. No significant side effects were observed.5 This study certainly is encouraging, with respect to the potential for the use of bilberry in diabetic retinopathy; however, more studies are needed. In addition, there has been a single case report suggesting that bilberry may potentiate bleeding risk when combined with other anticoagulants6; therefore, caution should be exercised with these patients.

Another supplement that has shown value in the realm of diabetic retinopathy is a standard extract of the French maritime pine bark, Pinus pinaster. Pine bark extract has been found to increase vascular resistance, specifically in the capillaries7.

A study of 24 patients with diabetic retinopathy was done using treatment with pine bark extract for three months. Investigators enrolled patients with early stages of retinopathy, characterised by mild to moderate retinal oedema. The treatment group showed statistically significant improvement in retinal oedema score and retinal thickness, as compared to the placebo group, which showed no substantial change. Central retinal artery laser Doppler flow velocity also showed a statistically significant improvement relative to the control group. This is a very positive indication of the therapeutic potential for pine bark extract, given this group of patients already had established disease with vision-threatening potential at baseline.8

Another investigation of 40 patients was done in a double-blind fashion, randomising patients to placebo or 50 mg pine bark extract three times daily for two months. Patients with diabetes, atherosclerosis and other vascular diseases involving the retina were enrolled in the study. The placebo group showed progression of retinopathy and decline of visual acuity over the course of the trial. The treatment group showed no deterioration in retinal function and some recovery in vision. The improvement in the pine bark extract-treated group could be visualized on ophthalmoscopy, fluorescein angiography and electroretinography. The authors postulate that these benefits are attributable to pine bark extract’s potent anti-oxidant, anti-inflammatory and capillary protective properties.9

Another study conducted a meta-analysis of five clinical trials. The authors concluded that pine bark extract was able to slow progression of diabetic retinopathy and improve visual acuity. Side effects were limited and mainly related to mild digestive distress.7

These studies lend hope for the potential of pine bark extract as a safe supplemental therapy in the prevention and treatment of diabetic retinopathy.

The supplementation with key vitamins and anti-oxidants such as bilberry and pine bark extract may help those struggling with diabetes mitigate the risk of retinopathy that ensues with years of disease. With the aforementioned research in mind, there is a role in discussing supplements with diabetic patients, especially those that are doing everything they can and still progressing. With the risk of vision loss at hand, the stakes are just too high.

References

1. Guides and Information – Diabetes Prevalence. Diabetes. (2019). Retrieved 9 February 2021, from https://www.diabetes.co.uk/diabetes-prevalence.html.

2. Jonas, J.B. & Sabanayagam, C. (2019). Epidemiology and Risk Factors for Diabetic Retinopathy. Front Diabetes27, 20-37. https://doi.org/10.1159/000486262

3. Shi, C., Wang, P., Airen, S. et al. (2020). Nutritional and medical food therapies for diabetic retinopathy. Eye and Vis 7, 33. https://doi.org/10.1186/s40662-020-00199-y

4. Gizzi, C., Belcaro, G., Gizzi, G., Feragalli, B., Dugall, M., Luzzi, R., & Cornelli, U. (2016). Bilberry extracts are not created equal: the role of non anthocyanin fraction. Discovering the “dark side of the force” in a preliminary study. European review for medical and pharmacological sciences20(11), 2418–2424.

5. Perossini, M., Guidi, G., Chiellini, S., & Siravo, D. (1987). Diabetic and hypertensive retinopathy therapy with Vaccinium myrtillus anthocianosides (Tegens) double blind placebo-controlled clinical trial. Ann Ottalmol Clin OculCXIII(12), 57-102. Retrieved 9 February 2021.

6. Aktas, Can & Şenkal, V. & Sarikaya, Sezgin & Karti, Sami. (2011). Bilberry potentiates warfarin effect? Turk Geriatri Dergisi, 14, 79-81.

7. Schönlau, F., & Rohdewald, P. (2001). Pycnogenol for diabetic retinopathy. A review. International ophthalmology24(3), 161–171. https://doi.org/10.1023/a:1021160924583

8. Steigerwalt, R., Belcaro, G., Cesarone, M. R., Di Renzo, A., Grossi, M. G., Ricci, A., Dugall, M., Cacchio, M., & Schönlau, F. (2009). Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy. Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics25(6), 537–540. https://doi.org/10.1089/jop.2009.0023

9. Spadea, L., & Balestrazzi, E. (2001). Treatment of vascular retinopathies with Pycnogenol. Phytotherapy research: PTR15(3), 219–223. https://doi.org/10.1002/ptr.853

The author of this article takes full responsibility for the accuracy of this article and is not in any way affiliated or employed by Intelligent Formula – any views stated is entirely the author’s view.

About the Author:

Dr. Sara Frye (née Gaib) obtained her Bachelor of Science from the University of British Columbia in Canada, after growing up in France. Her Doctor of Optometry (OD) degree is from Nova Southeastern University, where she received the Florida Optometric Association Presidential Award upon graduation in 2009. She went on to complete a post-doctoral residency at the University of California, Berkeley. She has a demonstrated passion for lifelong learning, going on to do her Master of Public Health (MPH) at the University of Arizona. She is also a Fellow of the American Academy of Optometry (FAAO).

Following residency, Dr. Frye was on faculty at Midwestern University for five years. She earned the rank of Associate Professor for her performance in teaching, research and service. Although her residency training was in the area of cornea & contact lenses, her current practice focuses on the diagnosis and treatment of ocular disease. She also does freelance medical writing in the realm of eye care.

Dr. Frye is passionate about travel, cooking, nutrition, health and fitness.

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