17
Nutritional Agents
Leo Paul Semes
Dietary supplements (vitamins and inorganic essentials)
fall under Title 21 of the Federal Register and must
comply with regulations for labeling and health claims.
The U.S. Food and Drug Administration (FDA) does not
require supplement (or drug) companies to submit
documentation that each batch of product contains
the labeled ingredients. Rather, manufacturers are
responsible for following Good Manufacturing Practices,
including product validation. Furthermore, dietary
supplement manufacturers may be subject to product
liability claims if impurities are found, they cause harm,
or they are improperly labeled. Advertising for dietary
supplements is regulated by the Federal Trade
Commission and also falls under The 1994 Dietary
Supplement Health and Education Act. Only “Structure-
Function” claims are allowed; that is, manufacturers are
prohibited from making claims that products prevent or
treat diseases.
Vitamins are organic compounds necessary for growth
and health and cannot be synthesized in sufficient quan-
tities for physiologic health by the body. Therefore they
must be obtained from food sources or supplementation.
Inorganic essentials (minerals are trace elements) are
required in much smaller quantities than vitamins. In
general, minerals and trace elements aid and support
physiologic functions and, like vitamins, must be obtained
from dietary sources.
The quantity of vitamins and minerals necessary for
normal physiologic functioning is the dietary reference
intake (DRI), which replaces the recommended dietary
allowance. The DRI is a set of dietary recommendations
and appears as “DV” (daily values). FDA regulations went
into effect in March 1999 that requires such labeling.The
DRI designation was formerly the FDA’s reference daily
intake. DRIs are reviewed by the Dietary Allowances
Committee of the Food and Nutrition Board of the
Institute of Medicine of the National Academy of
Sciences. Based on age and sex, these amounts are esti-
mated to provide for the physiologic needs of healthy
individuals. Vitamins are generally divided into two main
categories, fat soluble and water soluble.
A primer of the physiologic effects of the vitamins and
inorganic essentials can be found in Tables 17-1 and 17-2.
Vitamins are named alphabetically in the order in which
they were discovered or first reported.Therefore the list-
ing intersperses fat- and water-soluble members. Food
sources and deficiency states of vitamins are listed in
Tables 17-3 and 17-4.
It is important to remember that healthy individuals
can obtain sufficient vitamins and inorganic essentials
from food sources in the normal diet. Unfortunately, many
individuals fail to observe healthy eating patterns.A food
pyramid has been suggested recently by the U.S.
Department of Agriculture (http://www.mypyramid.gov/)
as a template. Other factors, such as lack of exercise, may
result in nutritional deficiencies as well as diseases such
as obesity, diabetes, and other chronic disorders.
Although absolute vitamin deficiency (e.g.,beriberi,pella-
gra, scurvy) may be relatively rare in developed countries,
malabsorption, poor nutritional habits, or other factors may
lead to such situations. In fact, many Americans may be vita-
min deficient based on recommended daily allowance or
recommended daily intake.The interested reader is referred
to the U.S. Department of Agriculture food and nutrition
information center for recommended daily allowance and
recommended daily intake (http://fnic.nal.usda.gov/).These
are also summarized in Table 17-1 as DRI values.
Supplementation intervention, therefore, must be
considered in specific deficiencies or recommended for
clinically proven efficacy. Vitamin A deficiency can be
treated readily, for example. The latter becomes difficult
to define in the face of studies that offer inconsistent,
incomplete, or even conflicting results.
Inorganic essentials and trace elements serve as cofac-
tors in a variety of physiologic functions. These are
summarized in Table 17-2.
The most significant vitamins from an ophthalmic
standpoint include the antioxidant vitamins (A, C, and E)
and are discussed with respect to function and deficiency
as well as potential clinical benefits. The B vitamin group
has been added because of their widespread representation
in foods and supplements.
295
296 CHAPTER 17 Nutritional Agents

Table 17-1
Vitamins and Selected Examples of Physiologic Effects

Vitamin Solubility Adulta DRI Physiological Effect(s)

A (retinol, vitamin A alcohol) Fat 5,000 IU Vision, cell differentiation

B1 (thiamin) Water 1.5 mg Cofactor in enzyme reactions
B2 (riboflavin) Water 1.7 mg Cofactor for tissue oxidation and respiration
B3/4 complex (niacin, niacinamide) Water 20 mg ATP synthesis; nicotinic acid may lower serum
cholesterol
B6 (pyridoxine) Water 2.2 mg Amino acid metabolism, nucleic acid synthesis
B9 (folic acid/folate) Water 400 mcg Amino acid metabolism
B12 (hydroxy/cyanocobalamin) Water 2.6 mcg Cell mitosis; detoxifies cyanide
C Water 120 mg Antioxidant
D (calciferol/cholecalciferol) Fat 400 IU Retinal function, Ca2+ metabolism
E (CVD) Fat 30 IU Free radical scavenger, protective against
tocopherol family
K (phytonadione) Fat 80 mg Blood clotting
a
DRI may vary for infants and pregnant women, for example.
ATP = adenosine triphosphate; DRI = dietary reference intake; IU = International Units.
Vitamins B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B8 (inositol), B10 (para-aminobenzoic acid), B11 (choline), lecithin, and
B15 (pangamic acid) are listed here for sake of completeness but not shown in the table.The reader is referred to http://www.acu-
cell.com for examples.

Zinc is present in a variety of dietary sources, includ- conjunctivitis, and photophobia. Therefore zinc is
ing seafood, liver, and eggs, and is an integral part of thought to be protective of vitamin A in the retina.
superoxide dismutase and catalase, two antioxidant Copper stores are decreased by excessive zinc inges-
enzymes. In populations at risk for developing age-related tion, so copper supplementation is essential with
macular degeneration (AMD), dietary zinc levels have concomitant zinc administration. Wilson’s disease is a
been shown to be decreased, and other researchers have genetic abnormality that leads to progressive accumula-
shown that those with zinc intake from dietary sources tion of copper that may manifest in the cornea (Kayser-
had a lower risk for some types of AMD. An early uncon- Fleischer ring). In addition, sunflower cataracts and renal
trolled pilot study of zinc supplementation demonstrated dysfunction may accompany the corneal sign. Copper
reduced visual deterioration in AMD.This probably repre- toxicity results when greater than 15 mg is administered.
sented the beginning of the era of clinical trials on the It is characterized by abdominal pain, nausea, vomiting,
effects of nutrition on visual function and ocular health diarrhea, myalgia, metabolic acidosis, coma, and death.
status. Zinc deficiency leads to a syndrome similar to vita- Contemporary scientific evidence lacks sufficient
min A deficiency because the conversion of retinol to reti- consistency to suggest that any single or multiple vitamin
nal requires zinc. Deficiency may result in night blindness, and mineral supplementation has specific beneficial
decreased color perception, hyperkeratinization of lid effect on ocular diseases such as AMD, cataract develop-
margins with lacrimal punctal stenosis, blepharitis, ment, or glaucoma. For example, lowering the intraocular
pressure in patients with ocular hypertension or glau-
coma has been demonstrated to slow progression.
Multivitamin and mineral supplementation has been
Table 17-2 shown to be of value in some cases of advanced stages of
Selected Inorganic Essentials and Their Physiologic AMD. No clear evidence exists to suggest that cataract or
Function glaucoma treatment may benefit from supplementation at
this time. Vitamin and mineral supplementation, there-
Inorganic fore, may benefit selected at-risk patients. Current clinical
Essential Adult DRI Range Physiologic Function data on the benefit of nutritional supplements are unclear
and, in some cases, contradictory. When confounders of
Copper 0.4–3.0 mg Monoamine oxidase patient age, sample size, supplement use versus intake
formation from foods, supplementation with a single or multivita-
Zinc 5–19 mg Carbonic anhydrase
min, presence of undisclosed or undiscovered underlying
activity
Selenium 10–75 mcg Protects against oxidative
disease processes, gauging disease progression, inconsis-
damage to hemoglobin tent outcomes measures, genetic and ethnic influences,
environmental factors such as smoking, and the unavoid-
DRI = dietary reference intake. able imprecision of data collection from retrospective
 CHAPTER 17 Nutritional Agents 297

Table 17-3
Common Food Sources and Selected Deficiency and Overdose Manifestations for Selected Vitamins of Potential Interest
to Ophthalmic Practitioners

Vitamin Food Sources Deficiency Overdose

A Eggs, liver, butter, cheese, whole milk, Nyctalopia, xerophthalmia Papilledema

fish, and green leafy or yellow vegetables
D Conversion in skin by exposure to Hypercalcemia
ultraviolet radiation
E Vegetable oils, wheat germ, leafy Neurologic abnormalities Vitamin K deficiency
vegetables, egg yolks, and legumes (including ophthalmoplegia)
K Green vegetables and synthesized by Reduced blood clotting None known
intestinal bacteria ability
B1 Fortified breads, cereals, pasta, whole Toxic optic neuropathy Beriberi
grains (especially wheat germ), lean
meats (especially pork), fish, dried
beans, peas, soybeans, nuts, and seeds
B2 Unrefined whole grains, liver, all meats, Light sensitivity, Nausea, vomiting,
eggs, green leafy vegetables, nuts, seeds keratoconjunctivitis sicca fatigue, anemia,
low blood pressure
B3/4 complex Same as B2 Pellagra Flushing (vitamin B3),
nausea, vomiting,
headache
B5 Same as B2 Insomnia, joint pains, edema Edema, severe fatigue,
joint pains
B6 Same as B2 Seborrheic dermatitis, Low blood sugar,
dizziness, migraine migraine, muscle
spasms
B7 Same as B2 Skin disorders, hair loss, Skin eruptions,
brittle nails increased blood sugar
B9 (folic acid/folate) Same as B2 Hemolytic and megaloblastic Headache
anemia
B12 Meat, dairy, eggs, seafood Toxic optic neuropathy Optic nerve atrophy
(in Leber’s disease)
C Citrus fruits, potatoes, tomatoes, Scurvy
strawberries, cabbage

Vitamins B8 (inositol), B10 (para-aminobenzoic acid), B11 (choline), lecithin, and B15 (pangamic acid) are not shown. The reader is
referred to http://www.acu-cell.com for additional details.

analysis are considered, interpretation of even the most
promising results may be clouded. Interpretation of any
single, large, well-designed and conducted clinical trial is
complex and has limitations. Caution is therefore
warranted when making generalized recommendations
for supplement use. The prudent clinician should recog-
nize that potential benefits are limited but that multivita-
min administration is comparatively safe versus certain
prescription and over-the-counter preparations.
The following discussion is intended as a guide for
those recommendations based on contemporary knowl-
edge of risks and benefits of vitamin and mineral supple-
mentation and considers the potential impact on three
ophthalmic disease states: glaucoma, cataract, and AMD.
These were selected for reasons of significance as well as
the body of literature available. In addition, specific treat-
ment recommendations for disorders resulting from
nutritional deficits are discussed. Finally, the role of
complementary and alternative medicine in ophthalmic
disorders is outlined.
CLINICAL USES OF VITAMIN AND
MINERAL SUPPLEMENTATION
Primary Open-Angle Glaucoma
Antioxidant intake for primary open-angle glaucoma
was reported in a prospective study. As part of the Health
Professionals Follow-up Study and Nurses’ Health Study,
a selected group of patients was evaluated using a food
frequency questionnaire to assess antioxidant intake
from foods and supplements. The glaucoma diagnosis
was confirmed by record review, and the authors found
no protective associations with antioxidant intake and
reduced risk of primary angle glaucoma progression.
The theory of antioxidant protection arises from
298 CHAPTER 17 Nutritional Agents

Table 17-4
Components of Ideal Ocular Nutritional Supplements

General Supplementation Recommended Daily Dosea

Vitamin C 40 mg
Vitamin E 40 mg
Lutein/ 12 mg
Zeaxanthine

Macular Degeneration Recommended Daily Doseb

Vitamin C 500 mg
Vitamin E 400 IU
Beta-carotene 15 mg (equivalent to 25,000 IU vitamin A)
Zinc (as Zn oxide) 80 mg
Copper (as cupric oxide) 2 mg

Cataract Recommended Daily Dosec

Vitamin C up to 1,000 mg

Ocular Surface Disorders Recommended Daily Dosed

Vitamin A (retinyl palmitate) 1,040 IU (range: 200–5,000 IU)

Vitamin C (calcium ascorbate) 90 mg (at least 50 mg)
Vitamin B6 (pyridoxal 5-phosphate) 6.3 mg (range: 2.0–20 mg)
Magnesium (magnesium sulfate) 20 mg (range: 10–50 mg)
Gamma linolenic acid (GLA) 750 mg (at least 300 mg)
Mucin 150 mg (range: 100–300 mg)
Cod liver oil 1.6 mg (range: 0.5–3.0 mg)
OR
Vitamin E 187 IU
Mixed tocopherol concentrate 20 mg
Marine lipid oil 1,541 mg
EPA 450 mg
DHA 300 mg
Flaxseed oil 1,000 mg
a
These doses are within the safe limits but may be below DRI values. (See Table 1 and Bartlett H, Eperjesi F. Ophthalmic Physiol
Opt. 2004; 24: 339-49.)
b
These doses are consistent with the AREDS formulation (see text).
c
For its antioxidant properties, this recommendation represents an upper limit.
d
United States Patent: 6,506,412, Issued: January 14, 2003; and TheraTears Nutrition®.
Investigations have supported as well as refuted various nutritional supplement components for the prevention of cataract forma-
tion, macular health supplementation (inner and outer layers), stabilization of visual field damage in glaucoma, and for maintaining
ocular surface integrity. A formulation that supports general ocular health would contain anti-oxidants in moderate amounts.
Supplements that target specific diseases would necessarily differ in composition.This table lists components of a general formula-
tion as well as components of specific formulations. In addition, selected products containing these ingredients are listed for refer-
ence.The reader is also referred to Tables 17-1 and 17-3.
Commercial products containing these ingredients are available from a variety of sources. Selected commercial brands are listed below.
B&L Ocuvite PreserVision (tablet) (Bausch and Lomb, Rochester, NY; www.bausch.com)
B&L (softgel) PreserVision (Bausch and Lomb, Rochester, NY; www.bausch.com)
EyePromise Restore (Zeavision, Saint Louis, MO; www.zeavision.com)
HydroEye, Macular Protect (Science Based Health, Carson City, NV; www.sciencebasedhealth.com)
iCaps (Alcon Laboratories, Ft.Worth,TX; www.alcon.com)
MaxiVision, MaxiTears (MedOp, Oldsmar, FL; www.medop.com)
TheraTears Nutrition (Advanced Vision Research,Woburn, MA; www.theratears.com)

oxidation-reduction agents being protective against
glutamate-induced toxicity.
Several characteristics of complementary and alterna-
tive medicine have been suggested to be favorable to
glaucoma treatment. Neuroprotective agents may offer
such properties as oxidative alterations of low-density
lipoproteins, scavenging of oxygen free radicals, and inhi-
bition of glutamate toxicity. The lack of persuasive
evidence from placebo-controlled clinical trials limits
recommendation of such potentially promising agents as

Ginkgo biloba, which improves cerebral blood flow.
Anecdotal reports of ginkgo and other potentially neuro-
protective agents may be of value in the future for adjunc-
tive glaucoma treatment. Lowering intraocular pressure
in patients with glaucoma continues to be the primary
modifiable risk factor worthy of intervention.
Cataract
Because the lens is avascular it might be expected that
vitamin or mineral augmentation would not protect
against cataract formation. The exception is vitamin C,
which is actively transported from the circulation to
ocular tissues and the aqueous and therefore is present in
greater concentrations than in blood. Selected epidemio-
logic studies regarding antioxidants and cataract have
suggested that single vitamins (vitamin C and E) may have
salutary effects on specific types of cataract formation
(nuclear, cortical, or posterior subcapsular) or their
progression.A more beneficial strategy may include multi-
vitamin and mineral supplementation begun early in life
and taken over long periods.
Although some individual trials present persuasive
evidence supporting efficacy or benefit from single or
multinutrient supplementation, universal guidance
remains obscure. The confounding factors associated
with clinical or epidemiologic studies are myriad. Not
every study investigates the same population. In some
studies benefit was associated with elderly populations
whose nutritional habits may be lacking. In other studies
efficacy was demonstrated among selected cases such as
among cancer patients. Some study populations are
assayed by “snapshot”serum samples. Other studies assess
single nutrients, whereas some include supplement
classes such as antioxidants or carotenoids. Many
researchers measure dietary intake using validated food
frequency questionnaires that harbor the limitation of
depending on patient recall. Studies are inconsistent in
whether any lens opacity, specific (nuclear, cortical, or
posterior subcapsular) cataract type, or cataract extrac-
tion is the endpoint. Finally, some studies use observa-
tional approaches, whereas others are prospective and
interventional.
Currently, retrospective analysis of auxiliary multivitamin
and mineral supplementation in the Age-Related Eye Disease
Study (AREDS) is under way. This will assess whether
concomitant Centrum© (Wyeth Consumer Healthcare) use
will delay the progression of lens opacities, as has been
suggested by a statistical appraisal of AREDS data. In fact,
AREDS Report No. 9 did not find any protective effect from
the AREDS formulations∗ against cataract formation. Risk
factors other than nutritional status/intake or in combina-
tion with supplement use may influence development,
progression, or visual impairment from cataract. Current
evidence offers only weak support at best for a recommen-
dation of multivitamin or other nutritional interventions as
protective against cataract formation or progression.
CHAPTER 17 Nutritional Agents 299
Age-Related Macular Degeneration
Necessarily, this term encompasses a variety of clinical
presentations. Drusen and pigment changes are recog-
nized as clinically observable risk factors for macular
degeneration, but indices in clinical studies include stages
of outer retinal changes (examiner specification) as well
as visual acuity (patient performance). For these and
other reasons mentioned above, making sense of even
carefully conducted studies makes deriving consistent
clinical recommendations a conundrum.
Fewer than 20 years ago high-dose zinc supplementa-
tion was reported to reduce significantly the risk of vision
loss in a short-term study that lacked a control arm. Since
then, nutritional interventions have become popular with
researchers as well as the general public. Unfortunately,
subsequent trials have failed to substantiate this initial
result.
Nevertheless, at least six randomized, double-blind,
placebo-controlled, intervention trials have assessed the
effect of vitamin or micronutrient supplements on AMD
risk.The consensus from these and other trials seems to
suggest a positive response of the retina as well as
improved visual performance from vitamin and mineral
supplementation such as the AREDS formulation (see
above). Specifically, the AREDS results should be inter-
preted as understanding that the formulation was effec-
tive in slowing the risk of progression of AMD in persons
55 years of age and older who had some macular changes
consistent with early age-related maculopathy. More
recently, substantiation of these results was reported on a
primarily white population as part of the Rotterdam Study.
An above-median intake of beta-carotene, vitamin C, vita-
min E, and zinc was associated with a 35% reduced risk of
AMD. Still other clinical research has demonstrated short-
term beneficial effects in small populations for lutein and
a combination of lutein and antioxidants in AMD.
Although these studies are promising as a basis for
specific clinical guidance, the application to general
populations is limited. The interaction of specific nutri-
ents, for example, remains unknown. In AREDS, only
patients in intermediate AMD, categories 3 and 4, showed
a treatment benefit.And, high-dose beta-carotene supple-
mentation may have adverse effects among smokers.
Because the treatment options are limited for patients
suffering from AMD and vision loss is rarely recovered,
this information should be portrayed to patients with
cautious optimism. Generally, well-nourished patients
with AMD may experience some reduced progression
∗
The specific daily amounts of antioxidants and zinc used by the AREDS
researchers were 500 mg vitamin C, 400 IU vitamin E, 15 mg beta-
carotene (often labeled as equivalent to 25,000 IU vitamin A), 80 mg
zinc as zinc oxide, and 2 mg copper as cupric oxide. Copper was added
to the AREDS formulations containing zinc to prevent copper deficiency
anemia, a condition associated with high levels of zinc intake. (Retrieved
March 28, 2007, from http://www.nei.nih.gov/amd/summary.asp#2)
300 CHAPTER 17 Nutritional Agents
with antioxidant and mineral supplementation.
Recommendations should be based on evidence that
many Americans may not, in fact, enjoy optimal nutrition.
Because supplements are available without prescription
(nor FDA scrutiny) in the United States, a balance needs to
be struck between probable benefits and potential risks.
Using the example of AMD, it appears that many
patients may benefit from the AREDS formulation as well
as a diet high in green leafy vegetables.The potential for
adverse effects (increased incidence of lung cancer)
among smokers, in particular, from ingestion of high
doses of beta-carotene has been suggested. Long-term
effects in healthy populations have not been reported.
Further characterization of an ideal formulation awaits
future research. One such study is currently under way.
AREDS II is evaluating the potential benefits of the antiox-
idants lutein/zeaxanthin as well as omega-3 long-chain
polyunsaturated fatty acids in delaying progression of
vision loss in AMD.
SPECIFIC VITAMIN AND MINERAL
SUPPLEMENTATION FOR
NUTRITIONAL DEFICIENCIES
Vitamin A Deficiency
Although rarely encountered in developed countries, vita-
min A deficiency remains a global public health problem.
The current World Health Organization recommendation
for vitamin A treatment in children 1 year of age and older
who are at risk (see Table 17-3) is one 200,000 IU oral
dose every 3 to 6 months for prophylaxis, and three such
doses for treatment and prevention of xerophthalmia.
Animal studies (rat model) have shown some improve-
ment in corneal epithelial function with topical vitamin
A supplementation. In human trials, evidence is contradic-
tory regarding the beneficial role of topical vitamin
A application. The apparent mechanism is reduction of
inflammatory components.
Folic Acid Deficiency
Folic acid deficiency may result in neural tube defects in
newborns. Folic acid is one of the few nutritional supple-
ments shown in clinical trials to be effective in prevent-
ing disease. Maternal prenatal supplementation with 400
mg/day folic acid reduced significantly the incidence of
neural tube defects in newborns, which indicates that
low maternal folate concentrations were associated with
these defects.
Toxic Optic Neuropathy (Cyanocobalamin)
Deficiency of cyanocobalamin, or vitamin B12, can result
in reduced visual acuity secondary to optic nerve
dysfunction. Causes range from malabsorption to alcohol
abuse. Treatment is with oral (1,000 to 2,000 mcg daily)
or intramuscular injections (1,000 mcg daily for 2 weeks
or 1,000 mcg twice weekly for 2 weeks followed by
weekly injections of 1,000 mcg for 2 months) of
cyanocobalamin. In chronic deficiency, lifelong treatment
is required.
Vitamin A in Retinitis Pigmentosa
The initial clinical trial examining the effects of vitamins
A and E on retinitis pigmentosa showed a modest decline
in progression of the disease based on electrophysiologic
findings. Recommendations from this and subsequent
trials have given rise to a treatment algorithm for retinitis
pigmentosa patients.Adults with early or middle stages of
retinitis pigmentosa should take 15,000 IU of oral vitamin
A palmitate every day and avoid high-dose vitamin
E supplements. Beta-carotene is not a suitable substitute
for vitamin A because it is not reliably converted to vita-
min A. People on this regimen should have annual mea-
surements of fasting vitamin A concentrations in serum
and liver function tests, although no cases of toxic effects
have been reported.
Omega-3 Fatty Acids in Dry Eye
Oral supplementation with omega-3 fatty acids may play
a role in relief of dry eye. Postmenopausal women are
most susceptible to the signs and suffer the symptoms to
a greater extent than other segments of the population.
Intervention may have a positive effect. Recent studies
also have demonstrated potential benefits on AMD,
as well.
SIDE EFFECTS AND
CONTRAINDICATIONS
Contraindications and adverse reactions associated with
the use of nutritional supplements, although rare, should
be considered. The risk of side effects from nutrients is
reduced compared with that from over-the-counter or
prescription drugs. On the other hand, interactions with
over-the-counter or prescription drugs may potentiate
these reactions. Perhaps the best known interactions are
those that interfere with clotting mechanisms. Because
nonsteroidal anti-inflammatory drugs and warfarin have
the therapeutic effect of blood thinning, caution is
advised in recommending vitamin C (doses > 1 g/day),
vitamin E, or Ginkgo biloba in these cases.Vitamin C may
interfere with normal metabolism of acetaminophen,
resulting in liver-damaging accumulation.
Clinicians should be aware that specific recommenda-
tions, such as the AREDS formulation, may not be recog-
nized as compounding doses of other over-the-counter
supplements.An example would be accumulating a toxic
dose of beta-carotene from using the AREDS formulation
along with additional sources of beta-carotene.
Other examples exist, and a complete enumeration of

supplements that the patient may be taking should be
evaluated to ensure that dosing remains within published
guidelines.
Other associations have been reported anecdotally.
These include competitive absorption among antioxi-
dants such as vitamin A and lutein/zeaxanthin. In general,
adhering to the DRI recommendations is safe for patients.
The DRIs as well as side effects of overdose of vitamins
are listed in Table 17-3.
The ocular side effects from herbal medications and
nutritional supplements have been reviewed recently.The
Dietary Supplement and Health Education Act of 1994
govern their manufacture and distribution. No efficacy or
safety standards are required to be met for marketing
some 700 available botanicals and 1,000 nutritional prod-
ucts.There may be significant variation in purity, potency,
and even content. Ocular side effects may range from
accommodative impairment, secondary to anticholiner-
gic effects (kava kava), to visual disturbances (licorice).
The World Health Organization has developed a classifica-
tion scheme to categorize such side effects. In the United
States a registry is available at www.eyedrugregistry.com.
One danger is that because herbal medications are
not regulated, few if any clinical trials are performed even
for safety or efficacy. One example is bilberry. Bilberry
fruit is used to treat diabetes and diabetic retinopathy.
Although animal models support the antioxidant role
in vasoprotection, no well-designed and conducted
clinical trials exist.The antioxidant effect may have bene-
fit in AMD, as well.The antioxidant efficacy in bilberry is
likely due to the tannin content, which is also found in
grapes.
Another danger of herbal medication supplementation
is that anecdotal information rises to a level of truth or
even dogma. Various estimates suggest that not only are
large sums of money ($60 billion worldwide) spent on
complementary and alternative medicine strategies, but a
large portion of the population (42% by some estimates)
uses them without proof and in many cases without
sanction or knowledge of the attending and treating
physician.
In summary, nutrients play a vital role in physiologic
functioning.The eye is no exception. Consequently, there
are potentially useful as well as harmful effects of supple-
menting vitamins and inorganic essentials.The least stud-
ied category, herbal medications, may hold great promise
for application in ophthalmic disorders but currently
pose too great a risk for wholesale recommendation. Even
though many of these compounds were discovered
centuries ago, current research has neglected an opportu-
nity to investigate their potential systematically. What
does appear to emerge is some benefit from antioxidant
supplementation against progression of AMD in selected
older individuals. The influence against cataract progres-
sion seems to be limited to vitamin C. Primary open-angle
glaucoma patients should be offered traditional intraocu-
lar pressure–lowering medications at the present time.
CHAPTER 17 Nutritional Agents 301
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