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Diabetic Retinopathy
By the Life Extention Foundation
This article contains the following sections:
Diabetic
retinopathy (DR), the leading cause of visual disability and blindness among
adults in the developed world, may affect as many as 20 million people.
Early detection and treatment are keys to preventing the vision loss and
blindness associated with the disease. Unfortunately, only about half of
those with diabetes have proper eye examinations on a yearly basis. It is
very important that diabetics have a dilated eye exam each year.
Retinopathy damages the retina by destroying the capillaries (minuscule
blood vessels connecting arteries and veins) that provide blood to the
retina, the light-sensitive nerve tissue that sends visual images to the
brain. With the onset of retinopathy, these vessels weaken or bulge with
microaneurysms that may hemorrhage, leaking blood or fluid into surrounding
tissue. When new blood vessels grow on the retina (and into the vitreous),
they can cause blurred vision and even temporary blindness. The real danger
lies in the scar tissue that ultimately forms, detaching the retina from the
back of the eye and often causing permanent loss of vision.
Chronically elevated blood insulin and glucose levels induce retinopathy.
Fortunately, research shows that even after having long-term diabetes,
lowering glucose has a positive effect on slowing the progression of
retinopathy. A study took place involving 834 people who were over the age
of 30 when they developed diabetes and who were approximately 65 at the
start of the study. A glycohemoglobin test was performed at the start of the
study, along with two follow-ups, 4 and 10 years later, which included a
physical and eye exam. Glycohemoglobin (also known as hemoglobin A1C) is the
best measurement of long-term glucose control. A high glycohemoglobin number
correlates with uncontrolled diabetes.
In non-insulin-treated participants, those that had the highest
glyohemoglobin levels at the start of the study had nearly a threefold
greater chance of having developed retinopathy after 10 years than those
with the lowest levels. In participants who already showed proof of
retinopathy at the start of the study, the presence of elevated
glycohemoglobin resulted in a fourfold greater risk of retinopathy
progression and a fourteenfold greater risk of proliferative retinopathy.
In those people on insulin with the highest levels of glycohemoglobin,
there was a 90 percent increased risk of developing retinopathy than those in the
lowest levels. The researchers concluded that controlling hyperglycemia even
later on in the course of diabetes will result in a significant decrease in
the incidence and progression of retinopathy and in the development of
visual loss (Klein et al. 1994). Published studies show that controlling
excess serum insulin is also important in preventing retinopathy (Raccah et
al. 1998; Boehm et al. 2002; Leslie et al. 2002).
There are additional precautions that can be taken to guard against the
development of retinopathies. Deficiency of vitamin B6, for instance, is a
proven cause of the disease. In order to rule out a nutritional deficiency
as the cause of retinopathy, a 10-week program is suggested that
incorporates a high-potency B-complex vitamin formula along with other
supplements that will be described in this protocol.
A newborn rat model of retinopathy was used to test the hypothesis that a
lack of the antioxidant superoxide dismutase (SOD) contributes to retinal
damage. The study concluded that delivery of SOD to the retina via
long-circulating liposomes was beneficial and suggested the potential value
of the restoration or supplementation of antioxidants in retinal tissue as a
therapeutic strategy (Niesman et al. 1997). It is difficult to provide SOD
directly to the retina, but adequate supplementation with nutrients, such as
zinc, copper, and manganese, provide the minerals needed for the formation
of SOD in the cells.
Another study investigated antioxidant activity in the lens and vitreous
of diabetic and nondiabetic subjects. Researchers found significantly
decreased glutathione peroxidase activity and lower ascorbic acid levels in
the lenses of diabetic patients, especially in the presence of retinal
damage. (Ascorbic acid is known to exert important antioxidant functions in
the eye compartment.) This study indicated that oxidative damage is involved
in the onset of diabetic eye complications, in which the decrease in free
radical scavengers was shown to be associated with the oxidation of vitreous
and lens proteins (Altomare et al. 1997).
Activities of enzymes that protect the retina from reactive oxygen
species were investigated in diabetic rats known to have developed
retinopathy. Diabetes significantly decreased the activities of glutathione
reductase and glutathione peroxidase in the retina. Activities of two other
important antioxidant defense enzymes--superoxide dismutase and
catalase--were also decreased (by more than 25 percent) in the retinas of diabetic
rats (Kowluru et al. 1997).
The study showed that diabetes is associated with significant impairment
of the antioxidant defense system and that antioxidant supplementation can
help alleviate the subnormal activities of antioxidant defense enzymes.
Administration of supplemental vitamins C and E for 2 months prevented the
diabetes-induced impairment of the antioxidant defense system in the retina
(Kowluru et al. 1997). Another study found no protective effect from
antioxidant nutrients for diabetic retinopathy and concluded that further
research is necessary to confirm associations of nutrient antioxidant intake
and the disease (Mayer-Davis et al. 1998).
A study assessed retinopathy in 60 oxygen-treated, premature infants and
their mothers. All 60 infants showed signs of acute oxidative stress. The
concentrations of methionine-cysteine in the plasma, as well as blood
selenium levels, were significantly lower in the premature infants who had
moderate retinopathy than they were in the oxygen-treated premature infants
without retinopathy. The mothers of the premature infants with retinopathy
showed the same pattern of deficiencies as their babies. Vitamin E treatment
of premature infants seemed to have a positive effect against the
development of retinopathy of prematurity (Papp et al. 1997).
The close correlation between the antioxidant capacity of the mothers and
babies suggests that supplementation with sulfur-containing amino acids
(methionine, cysteine) and folic acid during pregnancy might improve the
antioxidant capacity of premature infants. An antioxidant cocktail of
selenium plus vitamin E given to high-risk mothers (high risk factors
include advanced age, smoking, and pregnancy-induced hypertension) before
delivery might be useful in the prevention of retinopathy in premature
infants (Papp et al. 1997).
Other research examined the effect of propionyl-L-carnitine (an analogue
of L-carnitine) on retinopathy in rats with laboratory-induced diabetes. Findings pointed to a potential therapeutic value of propionyl-L-carnitine
for diabetic retinopathy (Hotta et al. 1996). Until propionyl-L-carnitine
becomes commercially available, taking 2000 mg a day of acetyl-L-carnitine
should be considered by those with retinopathy. (L-carnitine is a natural
substance that is found in meat. It is related to the B vitamins.)
Glycation of proteins has been shown to play a prominent role in the
development of many diseases related to diabetes, including atherosclerosis,
cataract formation, and retinopathy. Oxidation induced by glycation can
wreak havoc on the eye. Protein glycation occurs when sugar molecules
inappropriately bind to protein molecules, forming cross-links that distort
the proteins and consequently render them useless. High blood sugar also
increases glycation activity, which may also explain the various kinds of
tissue damage that characterize advanced diabetes. Diligently controlling
blood sugar is a major means of preventing or at least slowing the onset and
progression of diabetic retinopathy. Glycation appears to increase oxidative
processes, which may explain why both glycation and oxidation simultaneously
increase with age.
Strategies for the prevention of diabetic complications should therefore
aim to prevent both the effects of glycation and oxidative stress.
A drug called aminoguanidine has been used successfully to protect
against glycation (Guillausseau 1994). Compounds produced through metabolism
of sugars bind preferentially to aminoguanidine rather than to lysine
proteins. Thus, aminoguanidine is able to inhibit advanced glycation
end-product (AGE) formation and can help prevent the harmful development of
collagen cross-links and changes in the proliferation of mesangial cells.
Aminoguanidine used in the dose of 300 mg a day can specifically inhibit
glycation, as can the nutrients keto-glutarate and pyruvate. Studies have
shown aminoguanidine to be useful in slowing complications of diabetes, such
as retinopathy. (Aminoguanidine can also inhibit the formation of
atherosclerotic plaques.)
Carnosine is a naturally occurring antiglycation agent found in red meat.
In the lens of the eye, protein cross-linking is part of cataract formation. Carnosine eye drops have been shown to delay vision senescence in humans,
being effective in 100 percent of cases of primary senile cataract and 80
percent of cases
of mature senile cataract (Wang et al. 2000). The most widely used
antiglycating therapy is to consume orally 1000 mg a day of supplemental
carnosine.
One promising advanced glycation end product (AGE) breaker is ALT-711
(3-phenacyl-4,5-dimethylthiazolium chloride). ALT-711 is being developed by
the Alteon Corporation to reverse the degenerative effects on soft tissues
from diseases, such as diabetes and cardiovascular disease. It is currently
in Phase II trials. ALT-711 inserts itself into AGE crosslinks, separates
and cleaves the linked molecules, and releases the proteins. The safety of
ALT-711 and its efficacy in reversing age-related cardiovascular damage has
been confirmed in animals and in Phase I and Phase IIa clinical trials.
Alteon is planning a Phase IIb clinical trial. The randomized, double-blind,
placebo-controlled, clinical study will test the effects of multiple doses
of ALT-711 in improving isolated systolic hypertension. The trial will be
set up in 42 clinical sites and involve several hundred patients.
Countless studies demonstrate an association between consumption of
carotenoids with lowered risk of cancer and cardiovascular disease.
Carotenoids, especially lutein and zeaxanthin, have also been found to help
preserve eye health. Lutein is a pigment found in dark, green, leafy
vegetables, including spinach, kale, broccoli, collard greens, etc.
Zeaxanthin is found in fruits and vegetables with yellow hues, such as corn,
peaches, persimmons, mangoes, etc. They are often lumped together when
discussed or studied because they are structurally very similar, found in
many of the same foods, and both are present in the retina. Lutein and
zeaxanthin have been found to positively affect macular pigment density and
to help prevent age-related macular degeneration (AMD).
Although there are several hundred carotenoids to be found in fruits and
vegetables, only lutein and zeaxanthin are found in the retina (Schalch
1992; Yeum et al. 1999). Compared to other antioxidant concentrations found
in the eye, German researchers found that lutein and zeaxanthin did not
break down nearly as fast as lycopene and beta-carotene when exposed to free
radical or UV light induced oxidative stress (Siems et al. 1999). The
authors suggest that perhaps the slow degradation of lutein and zeaxanthin
may explain the strong presence of these carotenoids in the retina. Also,
the quick breakdown of lycopene and beta-carotene may suggest why these
carotenoids are lacking in the same retinal tissues.
Researchers have also found that lutein and zeaxanthin are more highly
concentrated in the center of the macula. There, the amounts of lutein and
zeaxanthin are much greater than their concentrations in the peripheral
region. At the Baylor College of Medicine in Houston, scientific
investigators demonstrated, using retinas from human donor eyes, that the
concentration of lutein and zeaxanthin was 70 percent higher in rod outer segment
(ROS) membranes where the concentration of long-chain polyunsaturated fatty
acids and susceptibility to oxidation is highest, than in residual membranes
(Rapp et al. 2000). The fact that lutein and zeaxanthin are particularly
concentrated in these parts of the eye suggests that they may act as a
shield or filter that helps to absorb harmful UVB light and dangerous
free-radical molecules, both of which threaten the retinal tissue (Moeller
et al. 2000; Bernstein et al. 2001).
Vitamin B12
(Cyanocobalamin, or hydroxycobalamin, a naturally occurring form) is
critical for several functions, such as folate metabolism, myelin synthesis,
and the normal development of red blood cells. A lack of this vitamin may
leave the optic nerve more susceptible to damage. Studies have suggested
that marginal vitamin deficiency plays an indirect but important role in the
development of diabetic complications (Anon. 1990).
Vitamin E
One study showed that reducing lipid peroxidation stress of the erythrocyte
membrane using vitamin E (alpha-tocopherol nicotinate) therapy may be useful
in slowing deterioration of microangiopathy in Type II diabetes mellitus.
The dose used in the study was 300 mg 3 times a day, after meals, for 3
months (Chung et al. 1998). In the August 1999 issue of the journal Diabetes
Care, Dr. George L. King and his colleagues reported that vitamin E
supplements normalized bloodflow to the retina and kidneys. Following a
4-month clinical trial in which subjects were given doses of vitamin E that
were 60 times the recommended daily allowance, kidney function improved and
blood flow to the retina was increased almost to the normal rate. Dr. King
is recommending a large follow-up clinical trial (Bursell et al. 1999).
Another study evaluated the use of antioxidants as a prophylactic for eye
disorders, such as macular degeneration, cataracts, retinopathy of
prematurity, and cystic macular edema. The study points to the positive role
of antioxidants in both experimental research and clinical observations
(KaLuzny 1996).
Green Tea
Green tea is another potent antioxidant that could be of use in the
treatment of retinopathy. The active compounds in green tea are chiefly
catechins. Powerful polyphenolic antioxidants, catechins are astringent,
water-soluble compounds that can be easily oxidized. They are a subgroup of
flavonoids, weak phytoestrogenic compounds widely available in vegetables,
fruit, tea, coffee, chocolate, and wine. The antioxidant potential of both
green and black teas, as measured by the Phenol Antioxidant Index, was found
to be significantly higher than that of grape juice and red wines. Green tea
also has anti-angiogenic properties, indicating that it could be used for
the prevention and possibly even the treatment of degenerative eye
disorders, such as diabetic retinopathy, that also depend on the development
of new blood vessels (Zigman et al. 1999; Thiagarajan et al. 2001).
Silibinin
An in vitro study showed that silibinin (milk thistle extract) can normalize
the degree of ribosylation and the sodium pump activity even in the presence
of abnormally high glucose levels (Di Giulio et al. 1999). A similar
protective effect of silibinin against ribosylation was found in the retina
(Gorio et al. 1997). Thus, silibinin may be able to decrease the extent of
diabetic neuropathy and retinopathy, two extremely serious complications of
diabetes. Considering that silibinin has also been shown to protect the
kidneys, another organ seriously damaged by glycation (kidney failure is a
frequent cause of death in diabetics), silibinin should be seriously
explored as an adjunct treatment in diabetes.
Retinopathy is a major cause of blindness among adults in the developed
world. Risk factors are diabetes (especially with elevated blood glucose
levels), vitamin deficiency, and old age. In retinopathy, the retina of the
eye is damaged when retinal capillaries bulge or burst, leaking blood or
fluid into the surrounding tissue. New capillaries that grow on the retina
(and into the vitreous) cause blurred vision or blindness. Permanent
blindness can result from retinal detachment caused by scar tissue. Prevention requires annual dilated eye exams and proper vitamin and nutrient
intake. Researchers conclude that improved levels of antioxidants in
pregnant women could help prevent retinopathy in their premature infants.
- Long-term antioxidant protection of the eyes can be provided by
taking 3 tablets 3 times a day, of Life Extension Mix and 1 capsule a
day of the Life Extension Booster formula. These two supplements provide
the alpha and gamma forms of vitamin E, lutein, minerals for the
formation of superoxide dismutase (SOD), such as zinc, manganese, and
copper along with potent B complex vitamins. Some people may also want
to take additional vitamin B6 (up to an additional 250 mg).
- Carnosine is an antiglycating agent that helps protect against the
damaging effects of glycation. As an oral supplement, two 500-mg
capsules daily are recommended. As an eyedrop, carnosine may help
prevent protein crosslinking in the retina. One to two drops daily of
carnosine eyedrops are recommended. Those with any kind of eye problem
may want to apply 1-2 drops several times a day.
- Zeaxanthin and lutein may help filter harmful UVB light and quench
free radicals that harm the retina. Suggested dose from diet or
supplements is 5 mg a day of zeaxanthin and 15-20 mg a day of lutein.
- Silibinin may help slow the extent of diabetic retinopathy; 250-500
mg a day is suggested.
- Green tea extract is a powerful antioxidant that has shown promise
in the treatment of degenerative eye disease; 600-700 mg of a 95
percent
polyphenol extract is suggested.
- Taking 2000 mg a day of acetyl-L-carnitine should be considered by
those who have retinopathy, particularly if on a vegetarian diet.
Contact the National Eye Health Education Program of the
National Institutes of Health, 301-496-5248.
Updated: 06/11/2003
Copyright © 1995-2008 Life Extension Foundation. All rights
reserved. Used by permission.
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