|
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 noninsulin 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% 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.
AN INTERESTING STUDY IN RATS
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.
ANTIOXIDANT LENS AND VITREOUS ACTIVITY
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).
DECREASED RETINAL ANTIOXIDANT ACTIVITY IN DIABETICS
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%) 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).
RETINOPATHY OF PREMATURITY
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).
THE ROLE OF L-CARNITINE
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
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% of cases of primary
senile cataract and 80% 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.
A Drug That May Reverse Glycation
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 cross-links, 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.
CAROTENOIDS AND THE RETINA
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% 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).
THE IMPORTANCE OF ADEQUATE VITAMIN STATUS
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.
CONCLUSION
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.
SummaRY
- 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, carno-sine may
help prevent protein cross-linking 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% 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.
For more information
Contact the National Eye Health Education Program of the National Institutes of Health, (301) 496-5248.
Product availability
Vitamin Depot Online.com,
Vitamin Depot Online.com, Super Carnosine, Brite Eyes II (carnosine drops), Super Zeaxanthin with Lutein, vitamin E, green tea extract, Gamma E Tocopherol/Tocotrienols, Silibinin Plus, vitamin B6, or ornithine alpha-ketoglutanate, calcium pyruvate and acetyl-L-carnitine can be ordered by calling (800) 544-4440 or by ordering online. Ask for a list of European suppliers of aminoguanidine.
| 
Print
PDF
Email
References
Suggested Products
