Statins vs. nutraceutical (Longevinex®) for vision threatening cholesterol deposits

In normal and diseased eyes cholesterol-like deposits (oxysterols) referred to as drusen accumulate over a lifetime behind the transparent retina of the eye, underneath a layer of cells that separate blood circulation (choroid) from the light-sensitive photoreceptors (rods and cones). With the aid of an ophthalmoscope drusen can be directly visualized by an eye physician as yellow-white deposits at the back of the eyes. [Retina, Oct 2010]

About 95% of adults exhibit drusen deposits in their retinas over their lifetime (British Journal Ophthalmology, March 1999), but certainly not as dense and profuse as seen in the male patient in this case report. In about 20-30% of eyes drusen deposits that begin in one eye can be seen in both eyes over a 5-year period. (British Journal Ophthalmology Jan 2017)

Oxysterol-laden (cholesterol) drusen deposits behind the retina were first detected in this patient at age 28. Progressive buildup of drusen continued to age 44 when measures to halt or reverse their accumulation were needed to save the patient's vision as these deposits approached the visual center (fovea) of the eye.

The critical nature of this case is that the patient only had functional vision in one eye. With non-functional vision from birth (20/800 vision on the lettered vision test chart) in his right eye and progressive accumulation of troubling cholesterol-like deposits called drusen in his left eye, he began taking a National Eye Institute-recommended antioxidant supplement in 2001 (AREDS Formula), later augmented with fish oil and coenzyme Q10.

The drusen-free area of his retina broadened but by 2009 his eye doctor wrote in his medical record "frightening central vision distortion" in his left eye. Straight lines looked wavy and irregular. These worrisome visual distortions moved around on a weekly and sometimes daily basis. A man with functional vision in only one eye was slowly losing his remaining sight and there was nothing that could be done about it.

With no proven treatment available, the patient began taking a statin cholesterol-lowering drug in 2012 with marked expansion of the drusen-free area of his retina, but the ominous visual distortions remained. An even more powerful statin drug was employed.

The sobering thought of losing his remaining sight caused the patient to embark on a weight loss program. He lost 51 pounds between 2013 and 2015. The male patient was out of options. He faced loss of independence and employment. He embarked on his own investigation and found an online source (EyeDoctorRicher.com) that address issues patients for whom all therapeutic measures had failed.

That is what I and my colleagues are commissioned to do - rescue patients from failing vision who have exhausted all treatment options - at the James A. Lovell Federal Health Care Facility in North Chicago, Illinois. We operate under compassionate care guidelines for these otherwise hopeless patients.

Our patient lived in Florida and did not attend our clinic. He embarked on a suggested treatment regimen after contact by telephone. In 2013 he added a self-prescribed nutraceutical (Longevinex®) to his daily pill regimen, eventually abandoning the second more powerful statin drug.

This provided a unique opportunity to compare the prior use of statins with a resveratrol-based nutraceutical.

While the drusen-free area continue to expand with the use of statins and a nutraceutical, the patient's vision didn't improve until the nutraceutical was employed. Thereafter retinal photographic images confirm the thickness and shape of his retina had normalized. The drusen-free area of his retina and almost doubled (from 5074 pixels to 9064 pixels). The patient's vision in his only functional eye remains stable at 20/20 on the eye chart over the past two years. The case presentation was published in a recent issue of the Journal of Advances in Medicine & Medical Research, Sept 2018]

Proposed Mechanisms

A dietary approach to maintaining retinal health should be of primary consideration. Resveratrol, known as a red wine molecule, is a molecular mimic of a calorie-restricted diet. However, monkeys fed a 30% reduced calorie diet did not exhibit fewer retinal drusen. [Open Longevity Science 2009] In our experience, resveratrol as provided in Longevinex® appeared to overcome whatever dietary factors are in play in our patients, even in advanced cases of disease.

Statin drugs have been proposed to address drusen deposits in human eyes and were shown to be modestly successful in a pilot study with 10 of 23 patients experiencing regression of drusen with up to 18 months of use. (EbioMedicine March 2016)

While statin drugs work by their ability to inhibit the enzyme (3-hydroxy-3-methylglutaryl-CoA reductase or HMG-CoA reductase) that is a precursor to cholesterol synthesis in the liver [Archives Neurology Sept 2010], so does resveratrol. [Biochemical Biophysical Research Communications Feb 2008] Resveratrol also reduces arterial plaque formation in arteries without lowering circulating cholesterol numbers. [International Journal Molecular Medicine Oct 2005] Resveratrol by virtue of its ability to chelate (bind to) copper thwarts hardening (oxidation) of cholesterol [Atherosclerosis Dec 2009], which then facilitates the disposal (efflux) of cholesterol, an mechanism that may be superior to statin drugs.

By comparison, resveratrol appears to have a superior safety profile compared to statin drugs. Statin drugs are associated with a number of undesirable side effects including liver toxicity, diabetes, cataracts, muscle aches and memory loss. [Expert Review of Clinical Pharmacology, Feb 2015] Because of diminishing benefits and problematic side effects, statin drugs may be inappropriate for older adults who comprise the vast majority of the population with macular degeneration. [JAMA Internal Medicine July 2017]

On the other hand there have been no serious side effects (hospitalizations, deaths) reported for resveratrol supplements and various human trials show resveratrol is well tolerated and safe. [Diabetes Obesity Metabolism July 2018; Experimental & Therapeutic Medicine Jan 2016]

The resveratrol pill that our subject chose had been previously reported by our clinical team to produce measurable improvements in vision among 16 of 17 otherwise helpless macular degeneration patients without side effect. [EurekAlert!, May 2012] It is the only resveratrol-based dietary supplement to have undergone toxicity testing as the Food & Drug Administration advises. [Food & Chemical Toxicology Sept 2013]

No cytotoxicity (cell killing) activity is noted in experimental studies using resveratrol in the animal lab when given in human equivalent doses ranging from 100-350 milligrams. In particular the resveratrol-based nutraceutical we chose to study exhibits no toxicity even when given in mega-doses in an experimental model of heart attack whereas the same mega-dose of plain resveratrol "kills" the rodent heart. [Experimental Clinical Cardiology, Winter 2010]

However, resveratrol overdoses have been reported to produce symptoms of Achilles heel tendonitis, skin rash, anxiety reactions and flu-like symptoms that resolve with dose reduction.

Emodin, a component of Giant Knotweed (botanical name: Polygonum cuspidatum) from which herbal resveratrol is extracted also contains emodin which has a laxative effect and can induce loose stool [Neurology, Oct 2015], a problem that is overcome with use of more purified extracts (as in Longevinex® (85+% resveratrol). [Evidence Based Complementary & Alternative Medicine 2015]

Resveratrol, a primary active component in Longevinex®, has only recently been proposed as a drusen-clearing agent. [PLoS One March 7, 2016] In this case, Longevinex® appeared to exert a more rapid and demonstrable improvement in vision than statin drugs.

Resveratrol as provided in a micronized, microencapsulated form (Longevinex®) has been detected in the human retina, meaning it traverses the blood brain barrier.

In an animal study Longevinex® closely mimicked the gene expression produced by life-long calorie restricted diet in just 12 weeks. [Experimental Gerontology, Sept 2008] Because of Longevinex®' superior gene-activating properties - 9-fold greater than plain resveratrol - other resveratrol offerings are not anticipated to produce such a rapid and demonstrative effect.

For this and other reasons Longevinex® was selected for scientific study for eye health in our eye clinic over 531 available brands of over-the-counter resveratrol. [Natural Medicines Comprehensive Database]

In yet another pilot study, Longevinex® was shown to reduce the time it takes for vision-producing chemicals at the back of the eyes to be replenished following bleaching with a bright light. [EurekAlert!, May 2017] Prolonged dark adaptation time is a proven indicator of future macular degeneration up to 5 years prior to the appearance of any disease signs or symptoms. The hope is one day macular degeneration will be detected at a pre-disease stage and completely prevented. Nutraceutical therapy may have a place in the eye clinic.

Dr. Richer has no financial interest in Longevinex®.

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