FOOD SUPPLEMENTS
Introduction
Nutrition are processes by which all living things, including human beings,
animals, plants and microorganisms, obtain and use substances in their sources of
food that are valuable and essential to their health. Nutrition is the end result of
ingestion, absorption and metabolism, the utilization of nutrients.
Studying nutrition involves identifying which nutrients create optimal wellbeing of the organism and which ingested substances may have harmful effects upon
one's nutritional status. Scientists and researchers through the ages have isolated the
vitamins, minerals and other substances necessary to human life and have
approximated the quantities required for well-being, that is, growth, tissue repair and
normal functioning, as well as therapy in the event that toxicity or deficiency of a
nutrient exists. Essential inorganic nutrients that promote the growth and maintenance
of living organisms are boron, calcium, chlorine, chromium, cobalt, copper, fluorine,
iodine, iron, magnesium, manganese, molybdenum, nitrogen, phosphorus, potassium,
selenium, silicon, sodium, sulfur, vanadium and zinc (1-4).
Essential organic nutrients, the main sources of carbohydrates, proteins and
fats that promote energy for living organisms requiring them are amino acids (the
precursors of protein), fatty acids, glucose and other simple sugars, purine and
pyrimidine and their derivatives (precursors of nucleic acids) and vitamins. Most of
the essential organic nutrients for human beings must be obtained from other living
organisms such as animals and plants. All the nutrients required for human life work
interdependently in order to metabolize and facilitate optimal functioning. For
example, the intake of calcium also requires a certain complementary amount of
magnesium so the calcium will be absorbed properly. An excess of calcium may be
responsible for a magnesium deficiency; in sum, the nutrients must be balanced. As
poor nutrition can induce disease, the state of disease can cause malnutrition (5-7).
Medicinal herbs generally refer to plant parts, sometimes ground, extracted, or
otherwise prepared, used for health benefits. Nutraceuticals, a more recent and more
general term, refer to a group of natural substances that includes certain herbs and
such products as cholesterol-lowering margarines and psyllium-fortified products that
are used as dietary supplements and regulated as foods (8-10).
Traditional systems of medicine have been used throughout the world for
centuries. Certain ancient systems, such as traditional Chinese medicine, Ayurveda
(the holistic system of medicine from India), and Tibetan medicine, are still used
extensively, particularly in their country of origin. In the United States, interest in the
therapies of such systems, particularly for the treatment of chronic illness, is growing.
These therapies, usually referred to as complementary or alternative medicine
range from medicinal herbs to acupuncture to massage. Most of them have not been
studied scientifically, and nearly all are unregulated (2).
The most commonly used alternative therapy is dietary supplements, which
include medicinal herbs and nutraceuticals. Because the use of dietary supplements is
widespread, the United States government passed the Dietary Supplement Health
Education Act (DSHEA) in 1994. It defines a dietary supplement as any product
1
(besides tobacco) that contains a vitamin, mineral, herb, or amino acid and that is
intended as a supplement to the normal diet. The act requires that the label of a dietary
supplement identify it as such. The label must state that the claims for the dietary
supplement have not been evaluated by the Food and Drug Administration (FDA).
The label must also list each ingredient by name, quantity, and total weight and must
identify the plant parts from which each ingredient is derived (11).
Most dietary supplements used in alternative medicine are derived from
plants; some are derived from animals. Because such dietary supplements are natural,
some people assume that they are safe to use. However, a substance is not necessarily
safe just because it is natural. For example, many potent poisons, such as hemlock, are
derived from plants, and some, such as snake venoms, are derived from animals.
Furthermore, almost all substances that affect the body-- whether dietary supplements
or drugs approved for medical use by the FDA have both wanted and unwanted
effects (side effects) (12).
Since Dietary Supplements are considered food by FDA, they do not require
the manufacturer to prove safety or effectiveness. While some supplements may be
good for health, others may cause harm. Food supplements are commonly used during
stages when during normal and healthy food pattern is not sufficient enough, like
pregnancy, age, stress and illness. The FDA defines dietary supplement as a product
people use in addition to the foods they eat (5). This would include:
I.
Vitamins
(e.g.: Vitamin B6, Niacin, Vitamin C)
II.
Minerals
(e.g.: Calcium and Iron)
III. Amino acid
(e.g.: Tyrosine, Creatine, Theanine, S-Adenosyl Methionine, L-tryptophan)
IV. Herbals
(e.g.: Ginko biloba, Gotu Kola, Astragalus, Bacopa, Cat’s claw, Echinacea,
Ginger, Chamomile, Kava Kava, St. John’s Wort, Alfalfa, Tofu, Ma Huang,
Ginseng, Milk thistle, Curcuma longa, Allium sativum, Linum usitatissimum,
Aloe vera and Oenothera biennis)
V.
Other products
(e.g.: Alpha-Lipoic acids, Essential fatty acids and Carnitine)
2
I. Vitamins
The word vitamin refers to organic compounds required in minute amounts to
catalyze cellular metabolism essential for growth or maintenance of the organism
(13). Vitamins are not utilized primarily as a source of energy or as a source of
structural tissue components, but rather as catalysts (14). Vitamins are micronutrients
that promote physiological processes necessary for continued life of the organism.
There are 13 vitamins; only three of these, vitamins D, biotin and pantothenic acid,
are manufactured by the body, and even these may not be sufficient for good health
(1). Therefore vitamins must be supplied by exogenous, or from outside, sources.
Vitamin deficiency results in a well-defined disease that is prevented or cured by
replacement of that vitamin. Physical and Metabolic Properties and Food Sources of
the Vitamins are listed in Table 1 (6).
Structure of Vitamins:
Water soluble Vitamins: L- ascorbic acid Dehydro-L- ascorbic acid
Vitamin B complex:
Thiamine (Vitamin B1):
Riboflavin (Vitamin B1):
3
Table 1: Physical and Metabolic Properties and Food Sources of the Vitamins
4
5
Nicotinic acid (Vitamin B3):
R= in NAD and R= PO3 H2 in NADP
Pyridoxine (Vitamin B6):
Panthothenic acid (Vitamin B 5):
Fat soluble Vitamins:
Vitamin E (α –tocopherol):
6
Vitamin A (Retinol):
Vitamin D (Cholecalciferol):
Vitamin K (Phytonadione):
Risk of free Vitamins:
Vitamin B6 Safe Upper Limit (15)
Similar reasoning led to an SUL (Safe Upper Limits) of 10 mg/day for vitamin
B6, even though this vitamin has been used with apparent safety, usually in doses of
50 to 200 mg/day, to treat carpal tunnel syndrome, premenstrual syndrome, asthma,
and other common problems. The SUL for vitamin B6 was derived from an animal
study, in which a dose of 50 mg/kg of body weight/day (equivalent to 3,000 mg/day
for a 60-kg person) resulted in neurotoxicity. The EVM (Expert group on Vitamins
and Minerals) reduced that dose progressively by invoking three separate “uncertainty
factors”:
1) by a factor of 3, to extrapolate from the lowest-observed-adverse-effect-level
(LOAEL) to a no-observed- adverse-effect-level (NOAEL)
2) by an additional factor of 10, to account for presumed inter-species differences
3) by a further factor of 10 to account for inter-individual variation in humans.
Thus, the neurotoxic dose in animals was reduced by a factor of 300, to a level that
excludes the widely used 50- and 100-mg tablets. The decision to base the SUL for
vitamin B6 on animal data (modified by a massive “uncertainty factor”) was arbitrary,
7
considering that toxicology data are available for humans. A sensory neuropathy has
been reported in some individuals taking large doses of vitamin B6.
Most people who suffered this adverse effect were taking 2,000 mg/day or
more of pyridoxine, although some were taking only 500 mg/day. There is a single
case report of a neuropathy occurring in a person taking 200 mg/day of pyridoxine,
but the reliability of that case report is unclear. The individual in question was never
examined, but was merely interviewed by telephone after responding to a local
television report that publicized pyridoxine-induced neuropathy. Because pyridoxine
neurotoxicity has been known to the medical profession for 20 years, and because
vitamin B6 is being taken by millions of people, it is reasonable to assume that
neurotoxicity at doses below 200 mg/day would have been reported by now, if it does
occur at those doses. The fact that no such reports have appeared strongly suggests
that vitamin B6 does not damage the nervous system when taken at doses below 200
mg/day. As the EVM did with other nutrients for which a LOAEL is known for
humans, it could have divided the vitamin B6 LOAEL (200 mg/day) by 3 to obtain an
SUL of 66.7 mg/day. Had the committee been allowed to evaluate both the benefits
and risks of vitamin B6, it probably would have established the SUL at that level,
rather than the 10 mg/day it arrived at through serial decimation of the animal data.
Niacin (nicotinic acid) Guidance Level (15)
Large doses of niacin (such as 3,000 mg/day) can cause hepatotoxicity and
other significant side effects. The EVM focused its evaluation, however, on the
niacin-induced skin flush, which occurs at much lower doses. The niacin flush is a
sensation of warmth on the skin, often associated with itching, burning, or irritation
that occurs after the ingestion of niacin and disappears relatively quickly. It appears to
be mediated in part by the release of prostaglandins. The niacin flush is not
considered a toxic effect and there is no evidence that it causes any harm. People who
do not like the flush are free not to take niacin supplements or products that contain
niacin. For those who are unaware that niacin causes a flush, an appropriate warning
label on the bottle would provide adequate protection. Granting, for the sake of
argument, that the niacin flush is an adverse effect from which the public should be
protected, the EVM's Guidance Level still is illogical. The committee noted that
flushing is consistently observed at a dose 50 mg/day, which it established as the
LOAEL. That dose was reduced by an uncertainty factor of 3, in order to extrapolate
the LOAEL to a NOAEL. Thus, the Guidance Level was set at 17 mg/day, which
approximates the RDA (Recommended Daily Allowances) for the vitamin. The EVM
also noted, however, that flushing has been reported at doses as low as 10 mg, so the
true LOAEL is 10 mg/day. Applying the same uncertainty factor of 3 to the true
LOAEL would have yielded a Guidance Level of a paltry 3.3 mg/day, which probably
is not enough to prevent an anorexic person from developing pellagra. As with
manganese, the EVM applied its methodology in an arbitrary and inconsistent
manner, so as to avoid being faced with an embarrassing result.
Vitamin C Guidance Level (15)
The EVM concluded that vitamin C does not cause significant adverse effects,
although gastrointestinal (GI) side effects may Level based on a NOAEL for GI side
effects. It is true that taking too much vitamin C, just like eating too many apples,
may cause abdominal pain or diarrhea. The dose at which vitamin C causes GI side
8
effects varies widely from person to person but can easily be determined by each
individual. Moreover, these side effects can be eliminated by reducing the dose. Most
people who take vitamin C supplements know how much they can tolerate; for those
who do not, a simple warning on bottles of vitamin C would appear to provide the
public all the protection it needs. Considering the many health benefits of vitamin C,
attempting to dumb down the dose to a level that will prevent the last stomachache in
Europe is not a worthwhile goal. However, as mentioned previously, the EVM was
instructed to ignore the benefits of vitamin C.
Granting, for the sake of argument, that there is value in setting a Guidance
Level for GI side effects, the EVM did a rather poor job of setting that level. The
committee established the LOAEL at 3,000 mg/day, based on a study of a small
number of normal volunteers. An uncertainty factor of 3 was used to extrapolate from
the LOAEL to a NOAEL, resulting in a Guidance Level of 1,000 mg/day. However,
anyone practicing nutritional medicine knows that some patients experience
abdominal pain or diarrhea at vitamin C doses of 1,000 mg/day or less, and the EVM
did acknowledge that GI side effects have been reported at doses of 1,000 mg. It is
disingenuous to set a NOAEL and then to concede that effects do occur at the noeffect level. To be consistent with the methodology it used for other nutrients, the
committee should have set the LOAEL at 1,000 mg/day, and reduced it by a factor of
3 to arrive at a NOAEL of 333 mg/day. The EVM was no doubt aware of the
credibility problems it would have faced, had it suggested that half the world is
currently overdosing on vitamin C. To resolve its dilemma, the committee used a
scientifically unjustifiable route to arrive at a seemingly politically expedient
outcome.
9
II. Minerals (1)
Inorganic elements required for a variety of functions including giving
structure to the skeleton, muscle contractions, blood formation, the synthesis of
protein and the production of energy. Minerals are found in red blood cells and cell
membranes. They are components of hormones and enzymes. Major or “macro”
minerals include calcium, phosphorous, sodium, potassium and others. Iodine, iron
and zinc are among the “trace minerals” found in very minimal quantities. Some
minerals found in even more minute concentrations possibly are necessary for health
(1). (Table 2)
Table 2: Minerals essential to health
Major or Macro Minerals:
Calcium
Chlorine
Magnesium
Phosphorus
Potassium
Sodium
Sulfur
Trace or Micro Minerals
Chromium
Copper
Iodine
Iron
Selenium
Zinc
Ultratrace Minerals (Probable essential to health)
Arsenic
Boron
Bromine
Molybdenum
Lead
Lithium
Manganese
Fluorine
Nickel
Silicon
Cobalt
Vanadium
Physiology and Sources of Nutritionally important Minerals are listed in Table 3 (6).
1- Calcium (1, 16 - 19)
Calcium is the most abundant mineral and the fifth most plentiful substance in
the body. The average adult contains from 2 to 3 pounds of calcium, of which 99
percent is found in the bones and teeth. The remaining 1 percent is found in the
circulatory system and aids in regulating various body functions. The newborn's
skeleton contains about 30 grams of calcium, most of which is deposited during the
third trimester of pregnancy. Calcium, which is absorbed from the small intestine,
requires the presence of vitamin D. Essential for healthy bone composition, calcium,
alone cannot increase bone mass after the age of 20. Although calcium supplements
probably do little to reduce the incidence of hip fractures in the elderly, there is little
downside to supplements. A French study in elderly women given 800 International
Units of vitamin D3 and 1.2 grams of calcium daily demonstrated more than a 40percent reduction in hip fractures. Results have been mixed in studies designed to see
if high calcium intake lowers blood pressure. While animal studies seem to indicate
that high calcium intake may protect against colon cancer, proof in humans is lacking.
10
Table 3: Physiology and Sources of Nutritionally important Minerals (6)
11
12
13
Deficiency
Osteoporosis is the most common and serious complication of inadequate
calcium intake or absorption. As calcium intake diminishes, calcium is resorbed from
bones, especially the spine and jaw, the first bones to show evidence of osteoporosis.
Vitamin D is essential for the utilization of calcium, and it may be prudent for women
at highest risk, such as those older than 65 who are housebound, reside in nursing
homes or live in areas where winters are long with minimal sun exposure, to take 200-400 I.U. of vitamin D daily. It has been found in several studies that women taking
thiazide diuretics for the treatment of hypertension had a reduction in the number of
hip fractures as high as 30 percent. It is known that these drugs interfere with the
excretion of calcium by the kidneys, and that the increased blood levels may result.
However, other studies dispute the findings and report only a modest 10percent increase in bone density for women on up to 10 years of thiazide therapy.
Regular weight-bearing, vigorous exercise seems to protect against osteoporosis
because stressed bone stimulates new bone production via osteoblast cells. But any
benefit is lost within one year of ceasing the exercise. Low blood-calcium levels cause
increased muscle sensitivity, resulting in muscle spasms, or tetany. Muscle cramps
occur when blood-calcium levels are very low and are particularly more common
during pregnancy. Infants fed undiluted cow's milk are at increased risk for tetany.
Recommended Daily Allowances
In 1994 The National Institutes of Health Consensus Development Panel made
new recommendations for calcium intake (see Table 4). This expert group
recommends a modest increase in calcium for most individuals that should not exceed
2,000 mg per day. Higher levels should be monitored carefully and may cause adverse
effects. Peak bone mass is probably attained from ages 11 to 24 years. Women older
than 50 who are on estrogen have a lower requirement equalivalent to premenopausal
women. Since calcium absorption from cow's milk is less efficient than from human
milk, formula-fed infants have an increased requirement.
Table 4: 1994 Recommendations by the national institutes of health consensus
development panel on calcium requirements (1)
Infants up to 6 months
Infants 6 to 12 months
Children I to 5 years
Children 6 to 10 years
Adolescents and young adults
(II to 24 years)
Men 25 to 65 years
Men older than 65 years
Women 25 to 50 years
Women older than 50 years
Pregnant or nursing women
Supplements Available:
400 mg/day
600 mg/day
800 mg/day
800-1,200 mg/day
1,200-1,500 mg/day
1,000 mg/day
1,500 mg/day
1,000 mg/day
1,000 mg/day with estrogen therapy
1,500 mg/day if not on estrogen
1,200-1,500 mg/day
14
Calcium supplements, generic or brand-name, are readily absorbed and best
when taken with meals. Dietary sources such as cheese, milk and yogurt are much
more expensive. Care must be taken to assure that sources of calcium used do not
contain toxic amounts of lead. Seventy brands of calcium supplements were analyzed
for lead content. Five categories of the supplements were identified: dolomite, bone
meal, refined- and natural-source calcium carbonate and calcium chelates. Lead levels
ranged from 0.03 mg/gram to 8.83 mg/gram. Twenty-five percent of the products
supplied daily lead quantities exceeding the federal Food and Drug Administration's
"provisional" total tolerable daily intake of lead for infants and children through age
6. Therefore, caution must be used to assure that calcium supplements, especially
those given to children with milk intolerance, have lead contents as low or lower than
the levels found in milk products.
2- Iron (20-23)
Iron is essential in humans for hemoglobin, cytochrome and other enzymes
essential for life. Its chief roles are in the transport of oxygen to the tissues and in
oxidation reactions in the cells. As much as 30% of iron is stored in the spleen, liver
and bone marrow as ferritin and hemosiderin. The recommended iron intake for men
and post-menopausal women is 8mg. The recommended iron intake for pre menopausal women is 18mg. There are 3 main kinds of iron supplements: Ferrous
Sulphate, Ferrous Gluconate and Ferrous Fumerate. Similar to calcium supplements,
when purchasing iron supplements, look for the elemental iron content, not the total
iron content. For instance, an iron supplement containing 200 mg of ferrous sulfate
provides 40 mg of elemental iron. Therefore, this iron supplement in this example
provides 40mg of iron. Many people may experience various gastrointestinal side
effects from taking iron supplements such as nausea, vomiting, constipation, diarrhea,
dark colored stools, and stomach distress. Some pharmacists suggested that Ferrous
Gluconate may cause less symptoms and is milder on stomach. To minimize side
effects, start with half the recommended dose, gradually increasing to the full dose. It
is also suggested to take iron supplements with Vitamin C-rich foods such as fruits or
fruit juice to maximize absorption.
Recommended Daily Allowances (RDA)
The RDA for iron is based on achieving iron stores of 300 mg to meet the
nutritional requirements for healthy people. That level of stored iron is sufficient for
several months of an iron-deficient diet. To maintain adequate stores, the RDA for
healthy menstruating adolescent and adult women is 15 mg daily. The RDA for
postmenopausal women and adult men is 10 mg daily.
The daily dietary allowance of 1.0 to 1.5 mg of iron per kilogram of body
weight should be sufficient for most infants. During pregnancy, an estimated total
requirement of 1,040 mg of iron is placenta and fetus. Although there is no need for
routine supplementation during the first trimester, additional iron is necessary durind
the later stages of pregnancy. An average increment of 15 mg daily throughout
pregnancy should satisfy the requirements of most women. A diet needs to contain 30
to 90 grams of meat, poultry or fish, all of which provide heme iron, a complex
molecule that is highly absorbed. Ascorbic acid (vitamin C) found in plant foods
improves the absorption of non-heme iron and is beneficial for people not consuming
15
adequate animal protein. However, there is probably no benefit to adding vitamin C to
the easily absorbed ferroussulfate form of iron found in most supplements.
Deficiency
As iron deficiency progresses, iron stores are at first diminished without
functional impairment. Eventually there is a reduction in quantity of erythrocytes, or
red blood cells, and hemoglobin, and the red cells become smaller than normal. The
World Health Organization has established that anemia occurs when hemoglobin
concentration falls 13 grams/decaliter in adult men and 12 grams in nonpregnant
women. During pregnancy 11, 10.5 and 11 grams of hemoglobin respectively, for the
first through third trimester, are the lower levels of normal.
Iron deficiency may result in reduced physical tolerance even before a fall in
hemoglobin is seen. Changes in several constituents of the immune system may also
occur, although resistance to infection is questionable. Children may experience
apathy, attention deficit, irritability and difficulty learning.
Iron is essential, with protein, vitamin E and zinc in the metabolism of vitamin
A, A high calcium intake may interfere with the absorption of iron and other minerals.
16
III.) What are Amino Acids (24-27)?
When you eat, the body breaks the food down into individual Amino Acids
which are then rearranged into a combination that is usable by the body.
Amino Acid Supplements: The Food and Drug Administration (FDA) advises
caution with amino acid supplements. Some have been reported to cause serious
injuries. You can get all the amino acids you need by eating healthful amounts of
foods rich in amino acids. Amino acids are the individual constituent parts of proteins.
Consumption of foods containing intact proteins ordinarily provides sufficient
amounts of the nine amino acids needed for growth and development in children and
for maintenance of health in adults. The safety of amino acids in this form is generally
not a concern. When marketed as dietary supplements, amino acids are sold as single
compounds, in combinations of two or more amino acids, as components of protein
powders, as chelated (a compound usually containing a metal ion) single compounds,
or in chelated mixtures. Amino acids are promoted for a variety of uses, including
body-building. Some are promoted for claimed pharmacologic effects.
The Federation of American Societies for Experimental Biology (FASEB)
recently conducted an exhaustive search of available data on amino acids and
concluded that there was insufficient information to establish a safe intake level for
any amino acids in dietary supplements, and that their safety should not be assumed.
FASEB warned that consuming amino acids in dietary supplement form posed
potential risks for several subgroups of the general population, including women of
childbearing age (especially if pregnant or nursing), infants, children, adolescents, the
elderly, individuals with inherited disorders of amino acid metabolism, and
individuals with certain diseases.
Serious Risks
At least two of the amino acids consumed in dietary supplements have also
been associated with serious injuries in healthy adults: L-tryptophan and
phenylalanine.
phenylalanine
L-tryptophan
There are two types of Amino Acids - nonessential and essential. The essential
ones can only be obtained from foods and the nonessential ones are manufactured by
the body.
17
The list of essential Amino Acids includes:







Histidine
Isoleucine
Lysine
Methionine
Phenylalanine
Tryptophan
Valine.
The nonessential ones are:











Alanine
Arginine
Asparagine
Aspartic acid
Cysteine
Glutamic acid
Glutamine
Glycine
Proline
Serine
Taurine
1- Tyrosine (28-30)
Tyrosine is an amino acid taken to help relieve depression. Like
phenylalanine, it helps the brain to produce the natural pain killing, energizing, and
mood-boosting chemicals dopamine and norepinephrine. It is taken to help relieve
anxiety and emotional lows associated with PMS, and it may play a role in the
treatment of drug detoxification and Parkinson's disease. It should be avoided by
anyone who suffers from high blood pressure. It comes in capsules.
L-tyrosine is a nonessential amino acid (protein building block) that the body
synthesizes from phenylalanine, another amino acid. Tyrosine is important to the
structure of almost all proteins in the body. It is also the precursor of several
neurotransmitters, including L-dopa, dopamine, norepinephrine, and epinephrine. Ltyrosine, through its effect on neurotransmitters, may affect several health conditions,
including Parkinson’s disease, depression, and other mood disorders. Studies have
suggested that tyrosine may help people with depression. Preliminary findings
indicate a beneficial effect of tyrosine, along with other amino acids, in people
affected by dementia, including Alzheimer’s disease. Due to its role as a precursor to
norepinephrine and epinephrine (two of the body’s main stress-related hormones)
tyrosine may also ease the adverse effects of environmental, psychosocial, and
physical stress.
L-tyrosine is converted by skin cells into melanin, the dark pigment that
protects against the harmful effects of ultraviolet light. Thyroid hormones, which have
18
a role in almost every process in the body, also contain tyrosine as part of their
structure.
People born with the genetic condition phenylketonuria (PKU) are unable to
metabolize the amino acid phenylalanine. Mental retardation and other severe
disabilities can result. While dietary phenylalanine restriction prevents these
problems, it also leads to low tyrosine levels in many (but not all) people with PKU.
Tyrosine supplementation may be beneficial in some people with PKU, though the
evidence is conflicting.
It is found in meats, fish, wheat, oats, and most other protein-containing foods
contain tyrosine.
2- Creatine (31-33)
Creatine monohydrate is popular as a muscle-building supplement among
athletes has helped in treating ALS (Amyotrophic Lateral
Schlerosis)/MND (Motor Neurone Disease) in animal studies.
Researchers at Harvard Medical School and Cornell University
Medical College found that mice (bred to develop ALS symptoms) fed
a diet high in creatine had the same amount of healthy musclecontrolling nerve cells as the mice in a control group. Creatine is a
natural body substance involved in the cellular transport of energy in
the body. Animal models of ALS/MND involve a genetic mutation in mitochondrial
genes, which regulate the energy of cells, and it is believed that similar defects occur
in humans. Animals on the creatine supplements showed complete protection up to
four months, when the disease would normally have begun to take hold. It has been
claimed that Creatine may be more useful for treating ALS/MND than
Rilutek/Riluzole. Creatine improves mitochondrial function and has been shown to be
neuroprotective in animal models of ALS and Huntington's disease.
In one study, creatine led to an increase in body mass, mainly through water
retention. A 28 day trial at 20 grams/day dose in 8 weight-lifters (a very small number
for a study), showed some increases in strength, weight and fat-free mass A summary
of 31 short term studies (using the drug for one week) indicated that creatine may
"modestly improve performance" in short duration (less than 30 seconds) bursts, but
not in sustained activity, and this was only in a laboratory setting. No definite benefits
were shown in actual field studies. Other studies showed "no consistent advantage
during aerobic exercise".
Adverse effects: One person with a kidney problem who took creatine
developed kidney failure. Most patients taking creatine had no short term side effects,
the long term effects are not known, and some patients reported some side effects
induding skin rash, shortness of breath, vomiting, diarrhea, nervousness, fatigue,
headache, muscle soreness and weakness, convulsions and heart irregularity. Whether
these effects were directly related to the creatine or not known.
Creatine may mildly improve performance in brief aerobic activities in the
laboratory. No data is available yet on long term safety. The potency and purity of
creatine sold as a dietary supplement is unknown since it is not under FDA control,
and many users tend to exceed the recommended doses.
19
Creatine does not replace conditioning, weight training, practice, and hard
work in achieving athletic success. If you use it, do not exceed dosage, and drink
plenty of fluids, and don't whine if you develop side effects 10 years from now,
because the long term effects are not known.
3- Theanine (34-36)
Theanine (L-theanine) is an amino acid found in ordinary tea leaves from
Camellia sinensis (also known as Theasinensis, hence the name theanine, pronounced
like tea-anene). It is also found in other species of Camellia and in the edible bay
boletes mushroom Xerocomus badius), but is otherwise rare in nature. L-theanine has
the reputation for promoting mental and physical relaxation-decreasing stress and
anxiety-without inducing drowsiness. In the beverage tea, it has an influence on taste
(reducing bitterness) and is said to counteract some of the nervous agitation that can
come with caffeine. Preliminary research, which needs to be carried much further
before more specific claims for benefits can be properly made, suggests that Ltheanine may be helpful for the following applications:

improving learning performance;

heightening mental acuity;

promoting concentration;

acting antagonistically against high doses of caffeine;

calming nervous agitation;

lowering blood pressure;

diminishing symptoms of PMS
It has been indicated by laboratory studies that theanine produces these effects by
increasing the level of GABA (gamma-amino-butyric acid), an important inhibitory
neurotransmitter in the brain. GABA serves a sedative function that brings balance to
excitability that can lead to restlessness, insomnia, and other disruptive conditions.
Theanine also appears to increase levels of dopamine, another brain chemical with
mood-enhancing effects, which can reduce blood pressure. To get adequate quantities
efficiently, L-theanine is synthesized, based on the way it is synthesized in the tea
plant. Theanine is a modification of the amino acid glutamine; with an ethyl group
added. It is simply made from glutamate as starting material:
Reaction:
A TP + l-glutamate + ethylamine yields: ADP + phosphate + l-theanine
20
This reaction takes place in tea roots; the theanine thus produced is transported
to the plant tops. The same reaction is used to synthesize l-theanine on a commercial
scale, using an enzymatic catalyst. There has been a developing interest, with
accelerated research that is still in the laboratory stage, into the potential of theanine
as an adjunct to cancer chemotherapy. In an abstract of one of his recent articles,
examples of the application for theanine was presented with a description of the
proposed mechanism: We have confirmed that theanine, a major amino acid in green
tea, enhances the antitumor activity of doxorubicin (DOX) without an increase in
DOX-induced side effects. We believe that the action of theanine is due to decreases
in glutamate uptake via inhibition of the glutamate transporter and reduction of
glutathione and DOX export from the cell. To increase our knowledge of the potential
clinical usefulness of theanine, we examined its effects on the antitumor activity of
cisplatin and irinotecan (CPT -II), which is known to be transported out of tumor cells
by the [same system]. Cisplatin decreased tumor volume in M5076 tumor-bearing
mice. Furthermore, the combination of theanine with cisplatin enhanced the decrease
in tumor volume as compared with the cisplatin-alone group. Tumor volume in the
CPT -II-alone group did not show a decrease, but the combination of theanine with
CPT-II significantly reduced tumor volume. The concentration of cisplatin in the
tumor was significantly increased by combination with theanine, and thus they
assume that it correlated with the enhancement on the antitumor activity by theanine.
On the other hand, changes in drug concentrations with theanine were not observed in
normal tissues, but rather it is indicated that theanine tends to reduce their
concentrations. Therefore, theanine enhances the antitumor activity not only of DOX
but also of cisplatin or CPT II. They found that theanine could block the export of
doxorubicin (Adriamycin)) from cancer cells by blocking the glutamate and
glutathione transporter mechanisms; the elevated level of the drug within cancer cells
strongly inhibits the tumor. At the same time, non-cancerous cells treated with the
chemotherapy drug plus theanine did not accumulate the drug. They have been
several studies of this nature, and if confirmed, it suggests that by either consuming
green tea (several cups per day) or taking supplemental l-theanine, the anticancer
effects of at least some of the chemotherapy drugs may be improved. Doxorubicin
also poses some threat to the cardiac tissue, for which coenzyme Q 10 is a
recommended protective therapy.
4- S-Adenosyl Methionine (SAM or SAM-e; pronounced "sammy")
It is an amino acid. SAM-e was discovered in 1952 in Italy, where it is
manufactured. Until recently, it was exceedingly expensive to produce, and therefore
unavailable to the public, although it is fairly well studied. It is manufactured in the
brain from another amino acid, methionine. SAM-e is the most active methyl-donor in
our bodies, meaning it donates methyl groups to other chemical compounds in your
body including neurotransmitters, changing them into other compounds. SAM-e is
then "recycled" through an ongoing re-methylation process.
SAM-e appears to be selectively beneficial in depressive disorders, but other
medicinal effects require more defined studies to prove its efficacy.
The majority of clinical trial evidence surrounds the application of SAM-e for
various depressive disorders, osteoarthritis, and fibromyalgia. Sample sizes of these
trials and the dose employed have varied considerably. Several reviews and at least
two meta-analyses have examined the available evidence surrounding SAM-e in the
21
therapy of depression for trials completed prior to 1994 and concluded that SAM-e
was superior to placebo in treating depressive disorders and approximately as
effective as standard tricyclic antidepressants. Much of this information exists in the
form of isolated case reports or solitary clinical trials. SAM-e appears to be well
tolerated, with the majority of adverse effects presenting as mild to moderate
gastrointestinal complaints. However, it is apparent that this agent is not without risk
of more significant psychiatric and cardiovascular adverse events. Information
documenting drug or food interactions with SAMe is very limited. Consumers should
be instructed to avoid unmonitored consumption of this dietary supplement until
sufficient discussion has taken place with their primary healthcare provider.
5- L-tryptophan
tryptophan
L-tryptophan is associated with the most serious recent outbreak of illness and
death known to be due to consumption of dietary supplements. In 1989, public health
officials realized that an epidemic of eosinophilia-myalgia syndrome (EMS) was
associated with the ingestion of L-tryptophan in a dietary supplement. EMS is a
systemic connective tissue disease characterized by severe muscle pain, an increase in
white blood cells, and certain skin and neuromuscular manifestations.
More than 1,500 cases of L-tryptophan-related EMS have been reported to the
national Centers for Disease Control and Prevention. At least 38 patients are known to
have died. The true incidence of L-tryptophan-related EMS is thought to be much
higher. Some of the individuals suffering from L-tryptophan-related EMS have
recovered, while other individuals' illnesses have persisted or worsened over time.
Although initial epidemiologic studies suggested that the illnesses might be
due to impurities in an L-tryptophan product from a single Japanese manufacturer,
this hypothesis has not been verified, and additional evidence suggests that Ltryptophan itself may cause or contribute to development of EMS. Cases of EMS and
related disorders have been found to be associated with ingestion of L-tryptophan
from other batches or sources of L-tryptophan. These illnesses have also been
associated with the use of L-5-hydroxytryptophan, a compound that is closely related
to L-tryptophan, but is not produced using the same manufacturing process that
created the impurities in the particular Japanese product.
The Food and Drug Administration (FDA) advises caution with amino acid
supplements. Some have been reported to cause serious injuries. You can get all the
amino acids you need by eating healthful amounts of foods rich in amino acids.
Amino acids are the individual constituent parts of proteins. Consumption of
foods containing intact proteins ordinarily provides sufficient amounts of the nine
amino acids needed for growth and development in children and for maintenance of
health in adults. The safety of amino acids in this form is generally not a concern.
22
When marketed as dietary supplements, amino acids are sold as single compounds, in
combinations of two or more amino acids, as components of protein powders, as
chelated (a compound usually containing a metal ion) single compounds, or in
chelated mixtures. Amino acids are promoted for a variety of uses, including bodybuilding. Some are promoted for claimed pharmacologic effects (27).
23
IV. Herbals (40-45)
In this transitional age when stress and environmental toxins seem to
accelerate the aging process, food supplements such as vitamins and herbs supply a
concentrated source of nutrition that can improve stamina, vitality, and energy.
Supplements can assist in prevention of or recovery from degenerative illness and
promote quality of life during the second half of the lifespan. Food supplementsconcentrated forms of plant life: weeds, flowers, trees-have been recommended by
healers for thousands of years. There is an ocean of information available on Western
herbs, Chinese herbs, and Ayurvedic herbs. Individual constitution is an important
consideration in the intricate Chinese and Ayurvedic systems. Self-prescription is
possible for some supplements such as multiple vitamins, vitamin C, and echinacea,
the benefits of which are well known and which have few side effects. It is imperative
for anyone who has a major health condition and is on medication to consult a
qualified professional. Supplements are most useful as an addition to a satisfying
whole foods diet and regular exercise. Herbal supplements in combinations offer the
advantage of treating both the symptom and the underlying condition. For example, at
the same time a diuretic effect is provided, other herbs in the formula are supporting
the improvement of kidney function. "Many herbs can be taken long term, but not all,
warns Darrell Brayboy, nutritional consultant in Winnetka, Illinois. For instance,
"Recommended use of goldenseal, effective natural antibiotic, is no longer than two
weeks because it can have a cooling effect on the digestive system."
A recent survey discovered that most people do not inform their prescribing
practitioner when they are taking a supplement. Combining herbals with medicines
can result in an adverse reaction where "double-dosing" can occur or a worsening of
symptoms in those with a chronic medical condition. That is why it is important to use
caution when taking supplements. It is always best to discuss use of an herbal or
supplement with your doctor or prescribing practitioner before starting it. The use of
herbals is on the rise. Some of the fastest growing herbal categories include the
following:

Herbals that increase circulation (e.g. Ginko biloba, Gotu kola),

Herbals used for calmative effect (e.g. Kava kava, Valerian, Chamomile,
Scullcap),

Herbals to lessen a cold flu symptoms and boost immunity (e.g. Echinacea,
Goldenseal),

Herbs for mild depression (e.g. St. John's Wort ).

Herbs for inflammation (e.g. Curcuma domestica , Chamomilla recutita).

Herbs for lowering cholesterol (e.g. Allium sativum, Zingiber officinale).

Herbs to treat hypertension (e.g. Valariana officinalis , Panax ginseng)
Be careful when using Herbal Supplements:

Herbals can interact with drugs used for anesthesia. The American Society of
Anesthesiologists recommends that all herbals be discontinued 2-3 weeks
prior to a scheduled surgery.
24

Herbals can adversely affect a pregnancy. Stop all herbals if pregnant or
breast-feeding.

Many herbals can interact with the anticoagulant Coumadin@ (also called
warfarin).
Some herbs can have an affect on how long it takes your blood to clot. Avoid
taking supplements of garlic, ginko biloba, ginger, feverfew, dong quai or
teas with coumarin while taking the blood thinner Coumadin@ as these herbs
can further prolong clotting times. Avoid goldenseal as this herb can shorten
clotting time. This may not be a complete list of interactions. More study is
needed. Check with your pharmacist and/or healthcare practitioner before
deciding to take any.


Don't give herbal remedies to children without first checking with the child's
pediatrician. There are many unknowns about the affect of herbs on children.

Don't take herbal products containing ephedra. Many deaths have been
associated with its use.

Many drugs interact with St. John's Wort, prompting the US Food and Drug
Administration to issue a health advisory. The FDA advises against using St.
John's Wort if also taking anyone of 50 other medications. St. John's Wort can
cause some drugs to be eliminated from the body too quickly, making them
less effective. This includes oral contraceptives, anti-cancer agents, heart
medications and drugs that fight HIV.

Ask merchants about standardization of a product and names of reputable
manufacturers. Check label for "dosage" which can vary depending upon the
strength of the product and the condition you are treating or preventing.

Know that combined use of herbs with medicines can have an unpredictable,
synergistic effect. Just because a product is "Natural" doesn't mean it's "Safe".
Keep a list of medicines and supplements you take and always share this
information with prescribing practitioners and your pharmacist.
Communication is key to safer use of medicines and herbal supplements. A
list of popular herbal supplements, common uses, possible reactions and
precautions to take in Table 5 (46).
Popular herbal supplements
1- Ginko biloba
Ginko biloba L. (Family Ginkogoaceae) is one of the
oldest living tree species, dating back to over 300 million
years. Extracts of the fruits and leaves of the Ginko tree
have been in China for over 5,000 years to treat lung
ailments such as asthma, bronchitis and also as a remedy
for various cardiovascular diseases.
Ginko biloba exerts ischemic protective and antioxidant effects through the
flavonoids that cause prevention of lipid peroxidation (47). Ginkgetin, a biflavone
isolated from Ginko biloba leaves, is a powerful antiinflammatory compound. It has
25
Table 5: A list of popular herbal supplements, common uses, possible
reactions and precautions to take (46)
Herb/
Scientific
Name
Common
Uses
To enhance
immune
Astragalus/
system
Astragalus
functioning
membranaceus
and improve
endurance
Body of
Evidence
Possible
Reactions
Increases natural
killer cells for cancer
patients and for HIV
patients. Polysacha
rides are probably
effective component.
It decreases blood pressure
due to vasodilation. It also
has a prolonged diuretic
effect.
Additional
Precautions/
Comments
Black
Cohash/,br>
Cimicifuga
racemosa
8 studies concluded
Treatment of
this herb can increase
PMS and
energy, improve
perimenopause
mood and control hot
discomfort
flashes.
Chamomile/
Chamomilla
recutita
ntiinflammatory.
Antispasmodic.
Sedative.
Antiulcer.
Dried flower heads
are used as a tea 3 or
more times a day to
promote relaxation.
Dong Quai/
Anelica
sinemsis
Relief of
menopause
symptoms and
PMS
A recent study found
dong quai root, if
used alone, was not
helpful. It is generally
used with other herbs
like black cohash.
Reacts with blood thinning
agents like Coumadin or
Do NOT use in conjunction with
Heparin, prolonging
anti-coagulant therapy. Do NOT
bleeding times.
use with any bleeding disorder.
Vasodilatory and antispasmodic effect.
Echinacea/
Anusctifolia,
palida or
purpurea
To relieve
upperrespiratory
infections like
colds, flu,
bronchitis.
Echinacea purpurea
may help shorten the
length of a cold but it
does not prevent it.
Used topically, it can
hasten wound healing
with herpes simplex
or eczema.
Limit use to 8 weeks.
Longterm use may actually NOT to be used in systemic
suppress the immune
disease (TB, Leukosis,
system so long-term use is collagenosis, MS, HIV, AIDS)
not advised.
Evening
Primrose/
Oenothera
biennis
To lower
cholesterol. To
reduce arthritis
inflammation.
To reduce
breast swelling
with PMS. To
treat MS
Has gamma linoleic
acid which has been
shown to lower
cholesterol.
Can accentuate
NOT recommended for patients
schizophrenic episodes or
with schizophrenia or for those on
precipitate seizure in those
drugs to treat seizure disorder.
taking epileptogenic drugs.
Feverfew/
Tanacetum
parthenium
To prevent
migraine
headaches
Studies vary from
70% reporting
reduction in migraine
severity to others
having no relief at all.
Stomach upset, mouth
ulcers. Feverfew can
interfere with blood
clotting.
Can cause upset stomach,
weight gain, headaches.
Use with caution if you
have high blood pressure
Long-term safety is not known.
Limit use to no more than six
months.
Do NOT use with antiocoagulant
therapy or with any bleeding
disorder. May cause rebound
headache. Does not relieve
migraine once it occurs.
26
Contains alphalinoleic acid (ALA) an essential omega-3
fatty acid. Plant
lignans increase
production of sex
hormone binding
globulin. Affects
vasoconstriction and
vasodilation
Flax seed/
Linum
usitatissimum
To promote a
healthy
immune
system. To
provide fiber.
To control
menopause
symptoms i.e.
night sweats.
Garlic/
Allium
sativum
Study results are
To lower blood inconsistent in
pressure.To
garlic's abilty to
lower
lower cholesterol.
cholesterol.
Can mildly lower
blood pressure.
Ginger/
Zingiberofficinale
To relieve
motion
sickness or
nausea; To
inhibit platelet
aggregation;
Cardiotonic
effect; To
lower
cholesterol.
Some
antibiotic
action.
Antioxidant
To enhance
memory and
slow dementia.
To improve
distance
Ginko/
Ginkgo biloba walking. To
improve
circulation
especially to
the brain.
Ginseng/
Panax
Drink plenty of water with
this food as it can be
binding. Contraindicated in
bowel obstruction or
patient with prostate
cancer.
Product must be fresh due to high
rate of oxidation. Avoid
concurrent use with laxative.
Avoid taking w/ oral medicines diminishes drug's effect
Can interfere with
hypoglycemic therapy
(used in diabetes) and with
anticoagulant therapies.
Other side effects include
nausea, vomiting and
diarrhea and a burning
sensation in the mouth.
Do NOT use in conjunction with
anti-coagulant therapy or antidiabetic therapy without
consulting your doctor. Do not use
with any bleeding disorder.
Studies conflict as to
effectiveness as antinausea remedy but
many claim it works
like dramamine to
May interfere with existing
fight motion sickness
cardiac, antidiabetic or
without the sideanticoagulant therapy.
effects. Herbalists
believe ginger is a
potent stomach
soother. Effects
gallbladder.
Do NOT use with anticoagulant
therapy or bleeding disorder.
Check with your doctor if being
treated for diabetes or a cardiac
condition. Fresh ginger root has
safe class 1 rating. Dried root is
Class 2 rating - not be used by
persons with gallstones.
Has been shown to
help people with mild
Alzheimer's but
unclear whether it
improves memory in
healthy people. Can Stomach upset, headache.
reduce swelling in
Allergic skin reaction.
hands and feet.
Evidence of
improved eyesight in
conditions related to
aging.
Consult with your doctor if taking
blood thinners including aspirin
and ibuprofen. Use with caution
with any anticoagulant and
antiplatelet medicines. Ginko can
interact with MAO inhibitors - be
careful!
Has been shown to be
useful in treatment of
breast cancer patients
- during
To have a
convalescence,
cardiotonic
physical or mental
effect. To help exhaustion, stress,
regulate blood inadequate resistance
sugar. To
to infections.
invigorate.
Potentiates many
other drug
actions(synergistic
effect) including
estrogens and steroids
Contraindicated for
individuals with high blood
pressure, acute illness,
those taking stimulants or
antipsychotic drugs. Can
interact with phenelzine.
Use with doctor's
supervision only if
hypoglycemic or in
diabetes to help regulate
blood sugar.
Do NOT use with anticoagulant
therapy. Ginseng is from a plant
that's hard to grow and expensive.
It takes 5 years for the root to have
herbal benefit. Look for at least
4% potency. There are many types
of ginseng. The leaf is cheaper but
ineffective.
27
Effect on wide
variety of ailments
that affect mucous
membrane lining:
decreases upper
respiratory symptoms
with cold or flu,
decreases gastritis,
decreases painful
menstruation,
decreases atonic
dyspepsia.
Do NOT use with high blood
pressure. Do NOT use with
Contraindicated in those
heparin as has coagulant activity
with high blood pressure. that opposes action of
May oppose action of
heparin.Sometimes used as a
heparin.
topical eye wash but consult with
your doctor before using in this
manner.
Goldenseal/
Hydrastis
canadensis
To decrease
mucosal
inflammation.
Gotu Kola/
Cenetella
asiatica
Has been shown to
have other actions
including antiinflammatory,
To improve
diuretic, digestant,
memory. To
CNS depressant,
treat venous
laxative, antipyretic.
insufficiency.
It increases the
To overcome
development and
fatigue, stress,
maintenance of blood
mental
vessels and
confusion.
connective tissue.
Can improve wound
healing if used
topically.
Contraindicated in
epilepsy. Side effects
include contact dermatitis Gotu Kola is a plant that elephants
and sensitivity to light. Do eat a lot of... and everyone knows
NOT use with anti-diabetic that an elephant never forgets.
drugs or cholesterol
lowering drugs.
Grape seed
extract/
Pine Bark
Contain OPCs
(Oligomeric Proantho
Antioxidant.
Cyanidins) which are
To improve
located in the skin
capillary
and seeds of grapes.
resistance with OPCs are unique in
varicose veins, that they have
cirrhosis of
property of
liver, ischemia, antioxidant in both
retinopathy.
lipid and aqueous
Antiphases.Effective free
inflammatory. radical quencher for
both positve and
negative charge
Antioxidant capacity 50
times greater than Vit E
and 20 times greater than
Vit C. Good source of
flavonoids. Flavonoids are
the most powerful
antioxidants found today.
Green Tea/
Camellia
Sinensis
To protect
against
chemically
induced tumor
initiation or
promotion.
Antioxidantlowers
cholesterol.
mild stimulant.
Contains good
antioxidant effects
with vitamins C & E.
Drink 3 cups per day
to decrease cancer
Contraindicated in persons
risk. Inhibits effects
who are sensitive to
of ultraviolet rays.
stimulants.
Blocks formation
nitrosamine. Used to
prevent athersclerosis
and
hypercholesterolemia.
28
Kava-Kava/
piper
methysticum
For nervous
anxiety, stress
and
restlessness.
Used to
enhance sleep
Useful with skeletal
muscle spasm and
tension. Kava-Kava
treats mild insomnia
conditions. It is also
useful as an
anesthetic on mucous
membranes to control
pain in oral
conditions. Topical
antifungal. Analgesic.
Potentiates many
other drugs
(synergistic).
Contraindicated in
endogenous depression.
Can cause mild GI
distrubances. Extended use
can temporarily cause
yellow coloration skin, hair
and nails.
Scullcap/
Scutellaria
laterifolia
To reduce
stress (nervine
tonic); Antispasmodic;
Hypotensive
Used for many years
in Soviet Union.
Used by soldiers,
deep sea divers,
rescue people
exposed to extreme
weather and stress.
Overconsumption has been
shown to cause CNS
stimulation, irregular pulse, Root is most important part of
confusion and hyperplant.
reflexia, but, no fatal
toxicity has been found.
Soy
Isoflavones
Soy isoflavones can
regulate calcium
To prevent
exchange across the
osteoporosis.
cell membrane and
To stimulate
calcium storage. May
mineralization
play a role in
Not to be used in
of bone. To
prevention of
conjunction with tamoxifen
regulate
atherosclerotic
therapy.
calcium
lesions. Natural plant
storage within
estrogens help
cell. Estrogen
modulate estrogen in
modulator
the body. May help
prevent breast cancer.
Kava-Kava (Piper methysticum)
has a Class 2d Botanical Rating
which means restrictions apply.
Avoid use with alcohol and/or if
taking other medicines prescribed
by a doctor. Do not use for more
than 3 months without medical
advice.
NEW: Benecol margarine made
from soy and other oils, claims to
lower blood cholesterol. No
known negative reactions. Used in
Europe for many years. Expensive
($14.98/lb). Natural soy products
have the same protective benefit
against osteoporosis as taking soy
isoflavones supplement. Foods
like soy puddings, soy nuts,
soymilk, tofu and other foods
made from soybeans are all
beneficial. High in plant estrogens.
Since St. John's Wort affects brain
chemistry and since long-term
effects are not known, it is
St. John’s Wort is
recommended that its use be
from Hypericum
Increased sensitivity to
limited to no longer than 3 weeks.
perforatum. It is an
light if taken in high doses.
Hastens elimination of many
anti-depressant
Can potentiate MAO
drugs, rendering them ineffective psychotropic. Affects inhibitors. Interacts with
including heart medicines, antimood and behavior. other medicines especially
cancer agents, drugs to fight HIV
Potentiates many
alcohol and over-theand birth control pills. For a
other drug actions
counter cold and flu meds
complete list of affected
(synergistic).
medicines, go to
www.fda.gov/cder/drug/advisory/s
tjwort.htm
St. John's
Wort/
Hypericum
perforatum
To treat mild
depression.
Has
Antibacterial,
Antifungal
properties.
Valerian/
Valerian
officinalis
Studies have shown it
produces less
grogginess in some
To relieve
people than
insomnia
prescription sleep
and/or anxiety
aids do. Blocks
arousal centers of
brain.
Headaches, restlessness.
Valerian root is not
associated with dependence
and potential addiction safer to use long-term
Do not take before driving. Don't
use with other sedatives. Do not
use with alcohol - potentiates its
effect. Valerian has a bad odor.
29
been shown to inhibit the release of arachidonic acid and also inhibit lymphocyte
proliferation induced by T-cell (48).
OH
OCH3
Ginkgetin
O
O
CH3O
O
HO
OH
OH
O
Significant reduction in joint inflammation in an animal model was achieved with
ginkgetin injections, but not with oral administration. These results indicate that
ginkogetin may be a potential antiarthritic agent (48).
Health risk following the proper administration of therapeutic dosage is not
recorded. Mild gastrointestinal compliant could occur as a side effect. Also, allergic
reaction has occasionally been documented after parenteral administration (47).
2- Gotu Kola
Gotu Kola, Centella Asiatica, of the parsley (Apiaceae)
family, is a ground hugging plant that grows in the wetlands of India,
Pakistan, Sri Lanka, Madagascar, and South Africa. The herb is
widely used to promote longevity, as noted by the Sri Lankan
proverb: “Two leaves a day will keep old age away.” This herb is also
known as centella and Indian pennywort. In India it is also sometimes
served as a vegetable.
Gotu kola has been used for thousands of years by central Asian herbalists. Sri
Lankan residents first recognized the potential for the herb after observing elephants
feeding extensively on the plant—and living up to 75 years. This herb has a storied
reputation for healing wounds, normalizing the nervous system, and increasing mental
clarity.
The plant is hypotensive and tonic. A group of saponins, known as
asiaticoside, madecassoside, and madasiatic acid, are the active constituents
responsible for gotu kola’s wound-healing effects. The saponins effectively inhibit the
production of collagen (material that makes up connective tissue) in hyperactive scar
tissue. This enables the structure of connective tissue to develop normally. Studies
also reveal that gotu kola used topically can aid in burns and wounds.
Gotu kola has been shown to normalize the nervous system and increase
mental clarity. Studies indicate the herb causes a steady, significant increase in blood
sugar levels. Because hypoglycemia (low blood sugar) has been documented to cause
fatigue and confusion, gotu kola’s action in this regard is vital. Gotu kola is also
higher in B-complex vitamins that any other plant yet studied. This is significant
because B-vitamins are essential to nervous system function and to the body’s ability
to convert food into energy. The saponins are involved in transmitting nerve impulses
to the brain’s cortex, thus enhancing all central nervous system functions. Additional
studies indicate gotu kola strengthens veins and capillaries, thereby improving overall
blood flow.
30
Gotu kola is known as a rejuvenating herb. It improves mental clarity, aids in
the function of the central nervous system, and promotes wound and burn healing.
Long a staple of the Orient, centella is now spreading west and gaining recognition as
a highly important medicinal herb.
Benefits
Gotu kola is used to minimize varicose veins, boost memory,
sharpen the mind in general, and stall memory loss related to
Alzheimer's disease. It has even shown promise in treating
scleroderma (an autoimmune disorder) and in controlling cellulite
because of its ability to reinforce the structure of connective tissue.
In one study, very good results appeared after three months in 58%
of the 65 patients taking gotu kola for cellulite.
Gotu kola has even been tested for reducing inflammation and improving liver
function in people with alcohol-induced cirrhosis and other conditions that involve
scarring and hardening of tissues in this large organ.
Treat burns, keloids, and wounds
When applied externally, gotu kola is believed to prevent or minimize
scarring, accelerating the healing of burns, keloids (overgrown scar tissue), and
wounds (including skin ulcerations and surgical incisions). Gotu kola may be even
more effective for burns when it's combined with echinacea, vitamins (A, C, E), and
zinc.
Minimize varicose veins
Gotu kola appears to enhance blood flow, increase the tone of the connective
tissue sheath that surrounds the veins, and maintain the suppleness of the veins. Study
results have been somewhat promising.
In a recent trial done in Italy, 87 people with varicose veins were randomized
to take either gotu kola or a placebo. At the end of two months, the participants taking
the herb showed measurable improvements in the functioning of their veins, while
those on the placebo did not experience any change in the tone or strength of their
veins. More research in this area is needed, however.
Boost memory and counteract Alzheimer's disease
In China, gotu kola has been used for centuries to heighten mental function.
Today, researchers are trying to determine if the herb has a role to play in improving
memory, enhancing learning capabilities, and perhaps restoring some of the memory
loss of Alzheimer's sufferers.
Results of a controlled animal trial indicate that the herb is effective in
enhancing learning. The animals given gotu kola for two weeks were able to learn and
recall new behaviors with greater ease than were those not given the herb. Also, in an
intriguing clinical study related to learning, 30 children with developmental
disabilities who received gotu kola for 12 weeks experienced significant
improvements in their attention spans and concentration skills.
31
Best Use
Gotu kola is available in tablets and tinctures, as well as in topical creams.
Although gotu kola causes changes on a cellular level in forty-eight to seventy-two
hours, clinical studies show that the body does not accumulate a maximum level of
asiatic acid, the chief active ingredient, until the herb has been taken for three weeks
or more (49-51).
3- Astragalus
(Astragalus membranaceus) It is known as Huang Qui in China
where it has been used for 2000 years. It has been used to raise vitality,
stop debilitating sweating, promote healing and tissue regeneration.
The raw root has been found to aid the body's resistances to infection,
promote diuresis, reduce swelling, promote suppuration (drain pus)
regenerate tissue, promote muscle growth and reduce chronic fatigue. Cured root is
said to replenish the vital energy and is used as a tonic to treat general weakness,
fatigue and lack of appetite. It contains more than 20 trace elements including
magnesium, iron, manganese, zinc, copper, rubidium, molybdenum and chromium
(52).
In animal studies, Astragalus was shown to enhance phagocytic activity and
increase super-oxide production and acid phosphatase activity of peritoneal
macrophages. When given to humans oral doses of the dried extract increased levels
of antibodies such as IgE and IgM. Increased levels of IgA and IgG in nasal secretions
were shown. Oral doses of Astragalus increased serum levels and conversion
percentage of lymphocytes when given to mice. It exerts an antiviral action, most
likely due to increased immunity and the enhancement of interferon production.
Studies have shown protective effects of Astragalus with para-influenza virus type 1
and Coxsackie B virus infection of myocardial cells in vitro and vivo after injection.
In vitro studies have confirmed the herb has antimicrobial effects against Shigella
dysenteriae, Streptococcus haemolyticus, Diploccus pneumonia and Staphylococcus
aureus. Astragalus is said to be adaptogenic, immune stimulating, tonic in nature,
diuretic and cardiotonic. It is useful for regulating the immune system, increasing
energy, reducing toxicity in the liver, lowering blood pressure, dilating blood vessels
and increasing the endurance of the heart. It has also been found to increase urine
flow, aid in recovery from bladder infection and help to neutralise fevers and improve
digestion. Polysaccharides in Astragalus, especially the polysaccharide fraction F3,
show considerable immune enhancing activity invitro. They have been found to
potentiate the immune mediated anti-tumour activity of interleukin-2 in vitro, improve
the response of T-lymphocytes from normal subjects and cancer patients in vitro,
enhance the natural killer cells activity of normal subjects and potentiate monocyte
activity. Triterpenoid saponins such as Astragalosides 1 to VIII, acetyl astragalosides
and astragenol have been identified. The root contains flavonoids, isoflavonoids,
sterols, a volatile oil and amino acids including GABA and l-canavanine. Clinical
studies confirmed the immune enhancing activity of the herb in vivo. The
pharmacological properties of Astragalus are varied and include immunopotentiating
effects, anti-bacterial and antiviral properties, the ability to promote nucleic acid
synthesis in the liver and spleen, hepatoprotective, anti-inflammatory activity,
cardiovascular tonic effects such as hypotensive and vasodilatory action plus a
possible blood glucose balancing action. The herb has also been found to increase
32
superoxide dismutase activity thus acting as a powerful antioxidant. Experiments
show Astragalus to be liver protective. In conjunction with Silybum marianum (St
Mary's Thistle) Astragalus with its antiviral and liver protective action, may help in
the treatment of Hepatitis C. The herb is useful in the treatment of kidney disease,
having the ability to reduce urinary protein in chronic and acute nephritis. These
effects appear to be mainly due to the saponins and polysaccharides in the herb.
Clinical studies have confirmed the herb's efficacy. Patients with low white
blood cell counts responded to treatment with Astragalus, maintaining 4000 cells per
ml while on the preparation. Prophylactic effect against the common cold was shown
for oral doses and nasal sprays and there was a decreased incidence and shortened
duration of infection.
Based on studies and clinical trials, astragalus has a number of uses in treating
or prevention of infection and impaired immunity, chronic bacterial or viral
infections, Chronic Fatigue Syndrome, chronic and autoimmune diseases, especially
nephritis.
As support for congestive heart failure, peptic ulcers, high blood pressure and
the common cold. As support, in conjunction with Korean Ginseng, for chemotherapy
and radiation therapy.
Toxicity of Astragalus root is very low with no side effects recorded in animal
studies. Doses of 12 x 400mg capsules for, several months have proven to beneficial
in treating some chronic illnesses such as Epstein Barr Virus and chronic fatigue (5355).
4- Bacopa
(BRAHMI) Bacopa monniera (L.) Pennell Scrophulariacea.
Herpestis monniera (L.) It is used in Indian ayurvedic
medicine for centuries to "improve blood circulation to the head". It
also affects the brain and nervous system, strengthening the nerves
and encouraging the smooth flow of energy along the nerves to and
from the brain. It improves coordination.
Constituents: Alkaloids, brahmine, and herpestine, 0-mannitol and a saponin. -A brain
tonic that improves memory and learning, imparting relaxation and restitution of
balance. Bacopa effects learning and memory retention and improves gross motor
coordination. It doesn't suppress motor efficiency. It is useful for treating nervous
deficit due to injury and stroke. Good as a general nerve tonic in nervous breakdown
and fatigue related conditions. Effective in the patient experiencing decreased strength
as a result nerve damage (56).
5- Cat’s Claw (57-59)
Primarily Cat’s claw (Uncaria tomentosa) is used to boost
immune function and documented to increase phagocytosis. The
chemical composition of cat's claw includes 17 different alkaloids,
quinovic acid glycosides, tannins, flavonoids, sterol fractions and
other compounds. Cat's claw contains a group of oxindole alkaloids
with documented biological activities.
33
Another form of Cat's Claw Uncaria guianensis is sometimes substituted for
or combined with U. tomentosa and there is some debate as to whether this is good,
bad or makes little difference. Some of the more expensive proprietary brands of
Cat’s Claw may actually have lower levels of useful compounds so it is important to
purchase this herb from a supplier that can verify the quality of the source material.
6- Echinacea (60-62)
This herb Echinacea pulp urea has been used for
centuries to treat colds, influenza, fevers and the like has been
shown to inhibit many viral infections.
As certain research suggests that AlS/MND may be
triggered by a virus, my own research recorded a worsening of
ALS/MND symptoms when my immune system was stressed by influenza or other
infections although it refers to CFS & AIDS, the following excerpt may be of interest:
"Extracts of Echinacea purpurea and Panax ginseng were evaluated for their
capacity to stimulate cellular immune function by peripheral blood mononuclear cells
(PBMC) from normal individuals and patients with either the chronic fatigue
syndrome or the acquired immunodeficiency syndrome. PBMC isolated on a Ficollhypaque density gradient were tested in the presence or absence of varying
concentrations of each extract for natural killer (NK) cell activity versus K562 cells
and antibody-dependent cellular cytotoxicity (ADCC) against human herpesvirus 6
infected H9 cells. Both Echinacea and ginseng, at concentrations> or = 0.1 or 10
micrograms/kg, respectively, significantly enhance NK-function of all groups.
Similarly, the addition of either herb significantly increased ADCC of PBMC
from all Subject groups. Thus, extracts of Echinacea purpurea and Panax ginseng
enhance cellular immune function of PBMC from normal individuals.
7- Ginger (63-66)
The major pharmacological activity of Ginger appears to
be due to gingerols and shogaols. It was found that ginger exhibit
carminative antiemetic, spasmolytic, peripheral circulatory
stimulant, anti-inflammatory, for headache and arthritis.
Powdered Ginger was a prophylactic against seasickness, motion
sickness, antiemetic and increase tones and peristalsis of
intestines. Zingerone had significant antioxidant effect on lowdensity lipoproteins. Other uses include for anorexia, bronchitis,
rheumatic complaints, and hypoglycemic, warming, diaphoretic and antineoplastic
effect. It has been shown that Ginger’s essential oil significantly suppressed formation
of DNA adducts by aflatoxin B1 in the microsomal enzyme-mediated reaction Ginger
is effective against both Gram- positive and Gram-negative bacteria and fungi. Ginger
inhibits Epstein –Barr Virus (EBV) activation.
O
OH
CH3O
CH3
HO
Gingerols
34
8- Chamomile (67-72)
The essential oil of both German and Roman Chamomile is
light blue in colour due to the terpenoid chamazulene. It is an artifact
formed during heating and comprises about 5% of the essential oil .It
has anti-inflammatory, antiallergic and antispasmodic properties.
Chamazulene affects free radical processes and inhibits lipid
peroxidation in a concentration- and time-dependent manner. Bisabolol comprises
50% of German Chamomile’s essential oil and a spasmolytic for intestinal smooth
muscle, anti-inflammatory, antipyretic and ulcer-protective. The flavonoid apigenin
possesses anti-inflammatory, sedative, anti-tumor, carminative and antispasmodic
properties. α-Bisabolol in the volatile oil of chamomile had the strongest activity
against Gram positive and Gram negative bacteria. Chamazulene also had strong
antimicrobial activity. Chamazulene, α-bisabolol, flavonoids and umbelliferone
displayed antifungal properties.
α-bisabolol
9- Kava Kava
methysticin
Kavain
Kava Kava is used in ceremonies and celebrations for its calming effect and its
ability to promote sociability (73). Kava Kava had attracted attention because it
contains a series of α-pyrones (Kava lactones) (74), which have anti-convulsive,
antiepileptic and local anesthetic effects (75). Unlike benzodiazepines (Valium, etc.)
Kava lactones do not appear to interact with γ-aminobutyric acid or its receptor sites
(76). Kava is also used to treat anxiety (77-78), inflammation of urogential system,
chronic cystitis, difficulties in urination, dysmenorrhea, migraine, rheumatism,
irritation of the respiratory tract, asthma pulmonary pains and skin diseases. Recent
research has shown that Kava extracts possess remarkable antimycotic properties.
Kavain possess bactericidal properties, especially against gonococcus and against
colon bacillus and blennorrhea (79).
An article in the Wall Street Journal recently referred to kava-Piper
methysticum as the latest herbal superstar. It has been used as a relaxing beverage for
centuries in the South Pacific. In tile United States, it is marketed in a variety of
forms, including powder-containing capsules. Its mechanism of action is not known,
but scientists assume it resembles that of benzodiazepines. Like St. John's wort, kava
is also thought to be metabolized by the cytochrome P-450 system and may have the
potential to interact with Reports of kava abuse have emerged over the past 15 years,
35
especially when used outside the structure of ceremonial rites in Aboriginal
communities. Excessive use of kava is associated with social problems as well as
neurologic side effects, including dystonic reactions, seizures secondary to
intoxication or withdrawal, and an acute neurologic syndrome characterized by
generalized choreoathetosis that responds to intravenous diazepam. A search of U.S.
medical literature yields little about kava and its ill effects. However, side effects may
include gastrointestinal upset, dizziness, ataxia, and sedation. Heavier use may
produce vision and hearing impairment, a yellow discoloration of the skin and nails,
as well as liver dysfunction (80). A side effect, usually seen only with long term,
heavy usage of the herb, is a scally skin rash called kava demopathy (80).
10- St. John’s Wort
Externally the oily St. John’s Wort preparations are
used as post-therapy treatment of acute and contused injuries
and first-degree burns. It is used internally for psychovegetative
disturbances, depressive moods, anxiety and nervous unrest.
The psychotropic effect attributed to hypericin suggests that the
pigment compound can cross Blood Brain Barrier possibly
treating neuropsychological symptoms such as dementia. The
herb can be used for local treatment of infected wounds and eczematous skin lesion.
Hypericin has been shown to have potent, broad-spectrum antimicrobial, antifungal
and antiviral activities (82-87).
Many herbs claim to boost mental health. One of the most popular "mood
elevators" is St. John's wort, Hypericum perforatum. The mechanism of action is not
fully understood; however, it is believed to affect several neurochemical pathways.
The herb acts as a weak monoamine oxidase inhibitor, perhaps involving serotoninspecific activity. Some evidence suggests an important role for gamma aminobutyric
acid receptors. This herb can cause mild fatigue and gastrointestinal upset. More
significantly, it can cause photosensitivity, as do some prescription antidepressants.
One of the active constituents in St. John's wort is hypericin, which is probably
responsible for photosensitivity, especially in people with light skin.
Patients should be advised to wear sunscreen. This side effect is usually
transient and resolves once the herb is discontinued. Little bas been written about the
drug interactions of herbs. Interaction between St. John's wort and some commonly
used medications such as alprazolam, nifedipine, sertraline, gabapentin, and
haloperidol are reported. Research appears to support these observations; findings
indicate that St. John's wort inhibits cytochrome P-450 isoenzymes. This interaction
could increase blood levels of the drugs that are metabolized by those isoenzymes.
Alternatively, some physicians warn that hepatic enzymes may he induced, thus
decreasing the bioavailability of some drugs. Such interactions will likely be clarified
as scientists learn more about the active constituents.
The potential for drug interactions is important because patients most
concerned about their mental health may also take prescription medications. Some
psychotropic medications work well together; however, it is not yet known whether
St. John's wort will prove to have a role in boosting the therapeutic effect of
prescribed antidepressants. Initial research suggests that clinicians should consider
drug-herb interactions when symptoms arise that may relate to drug or herh toxicity
and when counseling patients about the use of psychotropic herbs (88-90).
36
hypericin
11- Alfalfa (91-93)
Other single plant in the vast vegetable kingdom contains so
many health giving properties as are contained in the alfalfa herb-the
richest land grown source of nutritional trace minerals." Alfalfa is rich
in potassium, calcium, phosphorus, magnesium, chlorine and silicon-all
perfectly balanced. It also contains vitamins A, B, E and G, proteins
and some important amino acids without any fat content. Alfalfa is also
highly alkaline which works wonders for problems like fatigue and
tension. It strengthens the heart muscles, relieves arthritis, lowers blood pressure and
provides complete nutrition for the body. For those prone to catching infections,
alfalfa is ideal. Its ability to build up the body's immune system is quite phenomenal.
Its absorbable iron makes it a boon for anemia and its calcium prevents dental
decay. The high chlorophyll content in alfalfa makes it an elixir of youth. Alfalfa can
be consumed in many forms. The juice of fresh alfalfa leaves can be taken with carrot
juice and helps hair growth. The tea made of its seeds is delicious and is
recommended for arthritis. All you have to do is cook the seeds in an enamel or glass
pan for half an hour, strain the liquid and add honey. Take this tea four to five times a
day. It can also be refrigerated for two days. Alfalfa sprouts are very rich in nutrients.
Alfalfa seeds are available in most health food shops.
12- Tofu (94-96)
Also known as bean curd or soy cheese, tofu is low in cholesterol and calories,
and high in protein and vitamins. It is a complete food supplement that can be
consumed without any worry of side effects, unlike cottage cheese. It is prepared by
soaking soy beans overnight and then putting the contents through a machine
designed for making tofu. Tofu has worked wonders for high blood pressure. Tofu
can be a substitute for dairy products. Very few people are aware that 33 per cent of
Indians are lactose intolerant and hence should stay away from dairy products. Tofu
can be eaten as it is, mixed with fried or prepared in almost any way you prepare
cottage cheese.
13- Ma Huang (97-99)
Ma huang, also known as ephedra, is a Chinese
healing herb used for thousands of years. The ephedra
plant is a strange-looking, short, brushy shrub. Its stems
contain the active constituent from which the stimulant
ephedrine is now synthesized. The ephedra plant also
produces ephedrine's stereoisomer, pseudoephedrine.
Pseudoephedrine is the favored active ingredient in
nondrowsy OTC cold and sinus decongestants. Phenylpropanolamine (PPA) and
amphetamine are synthetic progeny. White PPA is used in decongestants, and it is a
37
popular ingredient of OTC appetite suppressants. Ephedrine was once used to treat a
variety of conditions, including asthma, hypotension, and depression. More effective
medications have largely replaced it for treatment of serious disorders, but it is still
available as an OTC bronchodilator, an anorectic agent, and an energy-enhancer.
Typical side effects of ephedrine and its relatives include increased heart rate and
blood pressure, insomnia, and anxiety. Serious problems most frequently involve the
nervous and cardiovascular systems. The FDA has received hundreds of complaints
about illness, and even death, associated with ephedrine use and is interested in
limiting the use of these products.
There is also a link between the ephedra plant and substance abuse. The Drug
Enforcement Administration has known for some time that ephedrine and
pseudoephedrine are used to produce the increasingly popular illicit stimulant
methamphetamine. Recently, cases of OTC abuse have been reported for ephedrine,
pseudoephedrine, and PPA. Patients at risk seem to include those with other substance
use disorders and eating disorders as well as night-shift workers and female athletes.
14- Ginseng (100-105)
Considered a yang (male) plant, ginseng is said to have
aphrodisiac properties. The root has been processed into a variety of
palatable forms such as capsules and tea. Research on ginseng by
scientists has shown that it also acts as a stress reliever. As a result,
ginseng is being promoted as an adaptogen (an agent that increases
overall resistance to the adverse effects of stress). Efforts to locate
ginseng led to Modem Bazaar, New Delhi, India, where two small bottles were
standing out against an array of various food supplements. Though no Indian
company is marketing pure ginseng, Dabur, the ayurvedic pharmaceutical company,
makes ashwagandha, or the Indian ginseng due to its similar properties, under the
brand name Stresscom. It acts as an immuno-modulator as well as helps in anxiety
problems. If there is a power drink, it must be wheatgrass juice. With chlorophyll,
beta carotene, more than 80 minerals, 18 amino acids and many vitamins, research has
shown that 1 kg of wheatgrass matches the nutritional value of 22 kg of ordinary
garden vegetables. Wheatgrass is generally consumed as juice which is a complete
food with regenerative and protective qualities. Its regular use improves perception
and increases mental and emotional calmness. It aids in digestion, prevents graying of
hair, skin diseases, asthma, arthritis and diabetes. In fact, because of its blood
purifying qualities, wheatgrass is used in the treatment of leukemia and some other
forms of cancer. The normal dosage of wheatgrass juice is 25 to 50 gm twice a day on
an empty stomach. It can be extracted from wheatgrass in a juicer. One disadvantage
is that it cannot be stored and has to be consumed immediately.
38
Wheatgrass can also be chewed and the pulp discarded. Though it is difficult
to find wheatgrass or its juice in the market, some rare clinics do sell wheatgrass
capsules.
Ginseng, the root of Panaxginseng (Araliaceae) is a well known folk medicine
in east Asia that has been shown to produce a variety of medicinal effects. Recent
studies showed that ginseng saponins, which are also called ginsenosides, were the
main molecular components responsible for the actions of ginseng. Ginsenosides have
a four ring, steroid-like structure with sligar moieties attached, and about 30 different
ginsenosides have been isolated and identified from the root Panax ginseng).
Some of the ginsenosides have opposing activities, e.g. ginsenoside Rg1 raises
the blood pressure and is a central stimulant, while ginsenoside RbI lowers the blood
pressure and is a central depressant, therefore use of Panax ginseng in hypertension is
questionable since they induce both vasodilation and vasoconstriction depending on
dose and target vessel.
ginsenosides
15- Milk thistle (106)
(Silybum marianum), a member of the Aster family, is a tall herb
with large prickly white-veined green leaves and a reddish-purple
flower that ends in sharp (often erroneously referred to as seeds)
contain up to 6 percent silymarin, the active flavonoid constituent
Silymarin's principal components are silybin, silycristin, and
silydianin. The primary investigational focus has been on silybin,
which is the most biologically active. A number of other flavonolignans have also
been found in the seeds including dehydrosilybin, desoxysilycristin, desoxysilydianin,
silandrin, silybinome, silyhermin, and neosilyhermin. In addition apigenin, silybonol,
and myristic, palmitic, stearic, and oleic acids have been reported. Technical Products
and lmnurities: Milk thistle is available at health food stores and pharmacies as well
as through direct-mail companies. Extracts are supplied as capsules, tablets, liquids,
powders and creams. Some of these milk thistle preparations are sold in combination
formulas with other herbs. In Europe, a water-soluble silybin compound is available
for use in intravenous infusion treatments.
39
Silybin (Flavonolignan)
Various preparations of milk thistle, especially the seeds, have been used
medicinally for over 2000 years. It was taken as a tonic, demulcent, anti-depressant,
and stimulant for milk production in nursing mothers. In homeopathy, a tincture of the
fruits is used to treat bronchitis, cough, gallstones, hemorrhage, jaundice, peritonitis,
uterine congestion, and varicose veins. Its use as a liver-protecting agent dates to early
Greek references. The plant is not mentioned in most American works on medicinal
plants until the end of the nineteenth century.
Currently the most important medicinal application of milk thistle is its use as
hepatoprotectant and as supportive treatment of chronic inflammatory liver disorders
such as cirrhosis, hepatitis, and fatty infiltration due to alcohol and toxic chemicals. It
has also been used in the treatment of liver damage by poisonous mushrooms.
Following the isolation of silymarin and the development of standardized
extracts in 1968, over 200 clinical studies involving over 4,000 patients have been
completed with milk thistle extracts. Modern clinical research on the hepatobiliary
effects of milk thistle began in Germany over thirty years ago.
For the treatment of liver disease (hepatitis, cirrhosis, toxin damage), the
recommended dose of milk thistle extract is 420 mg (silymarin) a day taken in three
divided doses. Suggested treatment periods range from 4 weeks to 9 months. When
milk thistle is used as a nutritional supplement or for preventive purposes, 210 to 280
mg (silymarin) a day is recommended.
16- Curcuma longa (107-121)
Curcuma longa L., Zingiberaceae is commonly known as
Tumeric. It is probably indigenous to Inia, it is cultivated today in
India and other tropical regions of Southeast Asia. It has been used
for hundreds of years as a spice and has long been known to possess
formidable antioxidant properties.
Curcumin, a diferuloylmethane is the active yellow pigment
in the rhizome of the drug.
Curcumin exhibits a variety of pharmacological effects including: Antitumer
activity, thus populations, like those in India, which consume through their daily diet
40
considerable amounts of tumeric (2-2.5 g/day), may be protected against several
mutagens/carcinogens present in the diet.
It reduces inflammation by lowering histamine levels and possibly by
increasing production of natural cortisone by the adrenal glands.
Curcumin
It protects the liver from a number of toxic
compounds.
It has been shown to reduce platelets from clumping
together, which in turn improves circulation and may help
protect against atherosclerosis, thus it appears to be safe in
geriatric patients who are prone to suffer from arthritis as
well as coronary artery disease.
In India it is used to treat obesity. It has a beneficial effect on the liver,
stimulating the flow of bile and the breakdown of dietary fats.
Modern research from Germany and India shows that turmeric protects against
gallbladder disease, stomach disorders, blood clots, menstrual problems and liver
ailments.
The chemical structure of curcumin was reported to be a derivative of methane
substituted by 2 ferulic acid residues but ferulic acid showed no significant antiinflammatory activity. This indicates that anti-inflammatory activity of curcumin is
not mediated through the release of ferulic acid in the system, but may be due to
characteristics of the diferuloylmethane molecule itself.
Ferulic Acid
The mechanism of anti-inflammatory activity of
curcumin is found to be multifactorial. It inhibited
lysosomal enzymes and was effective in inhibiting lipid
peroxide formation. Also formation of PGE2, TXA2
through the cyclooxygenase system and production of 5HETE via the 5-lipooxygenase pathway from arachidonis
acid were reduced in animals fed the curcumin diet.
A preliminary trial in people with rheumatoid arthritis found curcumin to be
useful for reducing inflammation and symptoms as pain and stiffness.
17- Arnica montana (122- 124)
Arnica montana L., Asteraceae, is found in Europe and in
central Asia. In folk medicine, it is used externally for in jury such
as traumatic edema, hematoma as well as rheumatic muscle and
joint problems. Furthermore, the drug is used for myocarditis,
arteriosclerosis, angina pectoris, sprains, cardiac insufficiency and
for hair loss due to psychological causes.
Helenalin, a sesquiterpene lactone, was isolated from A.
montana, has anti-inflammatory activity through inhibition of lysosomal enzymatic
activity in neutrophils at low concentrations, whereas cyclooxygenase activity was
inhibited at a higher concentration by helenalin and dihydrohelenalin.
41
Helenalin
and
dihydrohelenalin
have
antiinflammatory activity after intraperitoneal injection in
animals’ model auch as carrageenan induced edema and
chronic adjucant arthritis.
The alpha-methylene-gamma-lactone structure was
required for inhibitory activity in both models and the 4hydroxy group of helenalin was required for potency in the former model.
Helenalin
The sesquiterpene lactones are the poven sensitizing components and
prolonged treatment of damaged skin can cause edematous dermatitis with the
formation of pustules. In treatment involving higher concentrations, primary toxic
skin reactions with the formation of vesicles or even necrosis may occur.
The symptoms of overdose after oral ingestion of A. Montana include
dizziness, diarrhea, increased heart rate, cardiac rhythm disturbances and collapse.
Arnica poisoning has been caused death due to circulatory paralysis with secondary
respiratory arrest.
18- Allium sativum (125-128)
Garlic (Allium sativum Linne) (Fam. Liliaceae) has been used effectively as
food and medicine for many centuries. Water-soluble compounds (such as gammaglutamyl-S-allyl cysteine, gamma-glutamyl-S-methyl-cysteine, and gamma-glutamylS-propylcysteine) in raw garlic reduced cholesterol production in liver cells 16-29%.
However, water-soluble compounds(S-propyl cysteine, S-allyl cysteine, Sethyl cysteine), which are produced during the aging of garlic, reduced cholesterol
production 42-55% by prevention of cholesterol biosynthesis through inhibition of
hydroxymethylglutaryl-CoA reductase activity and other enzymes involved in
cholesterol biosynthesis, such as squalene mono-oxygenase and lanosterol-14demethylase. Thus, aging the garlic made its natural compounds even better.
Oil-soluble compounds, found mostly in garlic oil preparations, also reduced
cholesterol synthesis 10-25%. However, further inspection revealed that reduction did
not occur by inactivating enzymes that produce cholesterol in liver cells, but rather by
destroying the liver cells altogether. Cells naturally contain lactate dehydrogenase.
When the cells are damaged, they release this enzyme into fluids surrounding
them. Liver cells cultured with the oil-soluble compounds, diallyl disulfide, diallyl
disulfide, showed a significant increase in lactate dehydrogenase in the fluid
surrounding them, an indication of cells damage. Therefore, the reduction in
cholesterol seen by oil-soluble compounds was due to toxicity or cells death. Small
amount of these compounds however may be beneficial and non toxic.
Diallyl disulfide
42
Allicin, an odorous, unstable oil-soluble sulfer-containg compound in garlic,
this compound is very unstable, oxidative and is not absorbed by the body, even in
very hight amount. On other hand, S-allyl cysteine, an intriguing water-soluble
compound, effectively reduced cholesterol at a low concentration without toxicity. It
is stable, odorless, absorbed by the body.
Further, a number of non-sulfur compounds have also shown beneficial
effects. Saponins, for example, have been shown to reduce cholesterol, kill fungus,
and enhance the growth of bacteria.
19- Linum usitatissimum (129-131)
Populations with high intakes of alpha-linolenic acid (ALA) have a low risk of
cardiovascular diseases such as coronary heart disease (CHD) and stroke. ALA is an
essential omega-3 fatty acid found mainly in plants, for example, flaxseed (Linum
usitatissimum Linne) (Fam. Linaceae) is the richest source of ALA in north American
diet.ALA is the precursor of the long chain omega -3 fatty acids eicosapentaenoic acid
and docohexeenoic acid.
α-Linolenic acid
These long chain omega 3-fatty acids have been shown to reduce blood
triglycerides, increase blood HLD-cholesterol, reduce blood pressure, reduce platelet
reactivity and reduce neutrophil activity, all actions that help lower CHD risk, and its
effects appear to be distinct from those of EPA and DHA.
In clinical trials, ALA exerts positive effects on lipids. One study found that dietary
ALA was as effective as oleic acid and linoleic acid in lowering plasma total
cholesterol, LDL-cholesterol and VLDL-cholesterol level. The effect of flaxseed on
blood lipid was confounded by the fiber content of flaxseed. Flaxseed mucilage gum,
like other soluble dietary fibers, effect serum cholesterol level. Partially defatted
flaxseed was chosen because it is high in mucilage gums, but it has a lower ALA
content than full-fat flaxseed.
43
20- Aloe vera (1, 132-133)
A member of the Lily family, Aloe vera, also known as ‘’the
burn plant,’’ and whose name in Sanskrit, kumari, means goddess.
Indigenous to East and South Africa, the succulent aloe is grown in
the West Indies, tropical areas, some Mediterranean countries and in
the southwestern and southeastern United States, while the aloe
plant’s gel has long been used as a topical remedy for minor burns.
Herbalists and nutritionists often use crystallized aloe in extract form
as a laxative and ‘’cleanser’’ for the liver, kidneys and spleen.
In Ayurvedic medicine, aloe is considered a general liver tonic, a pain reliever
of muscle spasms associated with menstruation, a mild laxative, a blood purifier and
therefore beneficial to the liver, gallbladder and stomach.
However, the internal use of aloe, which contains a substance called
anthraquinone, has come under question because it has been known to cause
gastrointestinal cramping.
Two single blind studies have found that aloe vera juice helps lower blood
sugar levels in people with NIDDM. One study found that 1 tablespoon twice daily
notably improved the efficacy of the oral blood sugar-lowering drug glibenclamide.
The other study found that the juice by itself was effective .
21- Oenothera biennis (123)
Seed of Oenothera biennis contains about 14% fixed oil which
was commonly known as evening primrose oil. This oil is the
natural and the richest source of γ- linolenic acid. It contains
about 72% linolenic acid and 9% γ - linolenic acid.
Primrose oil is important for persons who do not get enough
essential fatty acids in their diet, have low thyroid function, or
have received radiation treatment.
γ- linolenic acid is rapidly converted in the liver into dihydo- γ- linolenic acid, the
intermediate precursor of PGE which is a potent anti-inflammatory agent.
Evening primrose oil is also used for neurodermatitis and in high cholesterol levels
and in the treatment of eczema.
COOH
CH3
-Linolenic acid
COOH
CH3
O
H
COOH
CH3
HO
HH
H
OH
PGE1
44
V. Examples for other products
1- Alpha-Lipoic acids (134)
Alpha-Lipoic acid is a supplement that works with enzymes throughout the body and
effectively speeds up the processes involved in energy production. It is also a
powerful antioxidant, therefore, it neutralises harmful free radicals. It is produced by
the body in very small amounts and is found in some of the foods we eat (spinach,
meats and brewer's yeast).
It is virtually impossible to take in enough Alpha-Lipoic acid via food so if we want
to benefit from we would need to take supplements.
Alpha-Lipoic acid affects every cell in the body and helps the body to utilize
all the B vitamins and it also boosts the efficacy of other antioxidants, including
Vitamins C. It is easily absorbed by the body making it a useful adjunct in the
treatment of a variety of conditions.
2- Essential fatty acids (130)
ESSENTIAL FATTY ACIDS (EFA's) are necessary for healthy neurological
function and general good health.
Commonly known as Omega 3, Omega 6 and Omega 9, this group
of fatty acids can be obtained from oily fish such as tuna, mackerel, etc.
and certain grains such as flax seed. EFA's are commonly known as "good
fats".
There are many supplements that will supply all three essential
fatty acids. These will usually be derived from fish or grain oils. There seems to be
little consensus as to the exact ratio of Omega 3,6 & 9 that are of therapeutic value in
treating neurodegeneration. It would be safe to say that supplementation with flax
seed and fish oils are likely to be beneficial for PALS. The inclusion of more fish,
fresh or canned, in the average Western diet is advised. Cod liver oil, flax seed oil,
olive, sunflower and canola oils are among the many sources of EFA's. All are
damaged by light, heat, oxygen, processing and contaminants and should be
refrigerated, protected from light and sealed tightly to avoid oxidation. Supplements
in gel capsule form may help overcome some of these problems. It is recommended
that a chosen supplement (or both supplement and diet) should supply Omega 3, 6, &
9. Dose rates will vary according to manufacturer, quality and age of product, storage
and other factors. Three servings of fish weekly and/or a high quality supplement
should provide useful amounts of EFA's in most cases
3- Carnitine (135)
Acetyl-L-Carnitine Some benefits of using supplementary Acetyl-L-Carnitine:
Improves nerve conduction velocity. Retards decline of Nerve Growth Factor (NGF)
Receptors. Stimulates and maintains growth of neurones within the brain both
independently of NGF and by preserving NGF. It inhibits degeneration of neurons
and reduces spasticity. It also increases responsiveness of neurotrophic factors and
reduces harmful, stress induced, cortisol levels. It as well inhibits Xanthene, oxidase
(a neuron damaging free radical). Now used to treat effects of ageing and age related
45
disorders such as alzheimer's disease. The suggested dosage is from 1500 to 3000mg
daily. Carnitine is available as the prescription medicine.
Potential and Specific Herb-Drug Interactions (136)
There have been relatively few reports of interactions with the coadministration of herbs and conventional drug therapies. Many of the interactions are
inconsequential. However, some could be serious depending on the herb quality,
concentration, and sensitivity of the patient (Table 6 and 7).
Twelve Supplements should be avoided (137)
If they are natural, they must be safe, right/ not so, say researchers at
Consumer magazine. In a report in the May issue, the consumer publication found a
dozen herbal supplements –some banned in Asia, Europe and Canada but widely
available in the United States that may cause cancer, kidney or liver damage and even
death (Table 8).
Liver Injury and Kava Products (138)
Letter to Health Care Professionals about FDA Seeking Information on Liver
Injury and Kava Products
The Food and Drug Administration (FDA) needs your help. The agency is
investigating whether the use of dietary supplements containing kava (also known as
kava kava or Piper methysticum) is associated with liver toxicity.
To help us determine whether there is a problem in the United States, we are
asking that you review your cases of liver toxicity to determine if any may be related
to the use of kava-containing dietary supplements. Products containing herbal extracts
of kava have been implicated in cases of serious liver toxicity in Germany and
Switzerland. Approximately 25 reports of hepatic toxicity associated with the use of
products containing kava extracts have been reported in these countries. Serious
hepatic adverse effects include hepatitis, cirrhosis, and liver failure. At least one
patient required a liver transplant. Based on their assessment of the adverse events
reported to them, the regulatory authority in Switzerland has prohibited the sale of
products containing the kava extract associated with the adverse effects. The German
authorities issued a proposal to remove all kava extract-containing products from the
market.
FDA is investigating whether the use of kava-containing dietary supplements
in the United States poses similar public health concerns. The agency has received
several reports of serious injury allegedly associated with the use of kava-containing
dietary supplements, with at least one report of hepatic failure requiring liver
transplantation in a previously healthy young female
FDA Guide to Dietary Supplements (139)
Bottled herbs like cat’s claw, dandelion root and blessed thistle; vitamins and
minerals are available in varying doses carry claims about relieving pain, energizing
and detoxifying the body, or providing guaranteed results. This store sells dietary
supplements, some of the hottest selling items on the market today. But even with the
business they generate, consumers still ask question about supplements:
46
Table 6: Potential Herb-Drug Interactions (136)
47
48
49
50
51
Table 7: Specific Herb-Drug Interaction (136)
52
53
54
55
56
57
58
Table 8: Twelve Supplements should be avoided (137)
NAME (ALSO KNOWN AS)
IN PRODUCTS
SUCH AS
DANGERS
REGULATORY
ACTIONS
DEFINITELY HAZARDOUS Documented organ failure and know carcinogenic properties
Aristolochic acid (Aristolochia,
birthwort, snakerroot, snakeweed,
sangree root, sangrel, serpentary,
serpentaris; asarum canadense, wild
ginger)
Vaxa PMS-Ease,
Shanghai Chinese
Herbal Company
Cardioflex (Guan
Xin Su He Wan),
Min Shan Brand
Long Dan Xie Gan
Wan
Potent human
carcinogen; kidney
failure, sometimes
requiring transplant;
deaths reported.
FDA warning to
consumers and
industry and import
alert, in April 2001.
Banned in 7
European countries
and Egypt, Japan,
and Venezuela.
VERY LIKELY HAZARDOUS Banned in other countries, FDA warning, or adverse effects in
studies
Comfrey (Symphytum officinale, ass
ear, black root, blackwort,
bruisewort, consolidae radix,
consound, gum plant, healing herb,
knitback, knitbone, salsify, slippery
root, symphytum radix, wallwort)
American Health &
Herbs Ministry
Asthma Formula
1040 Tincture
Abnormal liver
function or damage,
often irreversible;
deaths reported.
FDA advised
industry to remove
from market in July
2001.
Androstenedione(4-androstene-3,
17-dione, andro, androstene)
AST Sports Science Increased cancer
Andro100, SDIrisk, decrease in
Labs D-Bol
HDL cholesterol.
Methadrostenol,
Young Again
Nutrients
Androstene Dione
Chaparral (Larrea divaricata,
creosote bush, greasewood,
hediondilla, jarilla, larreastat)
Arizona Naturals
Chaparral tablets,
American Health &
Herbs Ministry
Bowel & Liver
Cleanser Tincture,
Larreacorp Ltd.
Larreastat
Abnormal liver
FDA warning to
function or damage, consumers in
often irreversible;
December 1992.
deaths reported.
Germander (Teucrium
chamaedrys,wall germander, wild
germander)
Nature's
Wonderland
Germander Herb
Powder
Abnormal liver
Banned in France
function or damage, and Germany.
often irreversible;
deaths reported.
Kava (Piper methysticum, ava, awa,
gea, gi, intoxicating pepper, kao,
kavain, kawa-pfeffer, kew, long
pepper, malohu, maluk, meruk, milik,
rauschpfeffer, sakau, tonga,
wurzelstock, yagona, yangona)
NutriBiotic
MetaRest, Ancient
Herbs Relaxit,
BlueBerry Matrix
Herbal Stress Relief
and Relaxation
Enhancement Tablet
Abnormal liver
function or damage,
occasionally
irreversible; deaths
reported.
FDA warned 23
companies to stop
manufacturing,
marketing, and
distribution in
March 2004.
Banned by athletic
associations.
FDA warning to
consumers in March
2002. Banned in
Canada, Germany,
Singapore, South
Africa, and
Switzerland.
LIKELY HAZARDOUS Adverse-event reports or theoretical risks
59
Bitter orange (Citrus aurantium,
green orange, kijitsu, neroli oil,
Seville orange, shangzhou zhiqiao,
sour orange, zhi oiao, zhi xhi)
Xenadrine EFX,
Metabolife Ultra,
NOW Diet Support
High blood
pressure, increased
risk of heart
arrythmias, heart
attack, stroke.
None
Healthgenesis.com
Organ/glandular extracts
(brain/adrenal/pituitary/placenta/other Brain Concentrate
gland "substance" or "concentrate") capsules, Plymouth
Bell Labs
Multigland-F Aspen
GroupGlan-Fem
Plus
Theoretical risk of
mad cow disease,
particularly from
brain extracts.
FDA banned highrisk bovine
materials from older
cows in foods and
supplements in
January 2004.
(High-risk parts
from cows under 30
months still
permitted.) Banned
in France and
Switzerland.
Lobella (Lobelia inflata, asthma
weed, bladderpod, emetic herb,
gagroot, lobelie, indian tobacco,
pukeweed, vomit wort, wild tobacco)
Nature's Way
Lobelia Herb
respiratory tonic,
Nature's Way
Breathe-Aid,
American Health &
Herbs Ministry
Asthma Formula
1040 Tincture
Breathing difficulty, Banned in
rapid heartbeat, low Bangladesh and
blood pressure,
Italy.
diarrhea, dizziness,
tremors; possible
deaths reported.
Pennyroyal oil (Hedeoma
pulegioides, lurk-in-the-ditch,
mosquito plant, piliolerial, pudding
grass, pulegium, run-by-the-ground,
squaw balm, squawmint, stinking
balm, tickweed)
Nature's Answer
Pennyroyal Herb
Extract, Nature's
Wonderland
Pennyroyal Herb
capsules, American
Health & Herbs
Ministry Pennyroyal
Tincture.
Liver and kidney
None
failure, nerve
damage,
convulsions,
abdominal
tenderness, burning
of the throat; deaths
reported.
Scullcap (Scutellaria lateriflora, blue
pimpernel, helmet flower, hoodwort,
mad weed, mad-dog herb, mad-dog
weed, quaker bonnet, scutelluria,
skullcap)
Solaray Skullcap
Abnormal liver
None
Capsules, American function or damage.
Health & Herbs
Ministry Appetite
Stimulant Formula
Tincture
Yohimbe (Pausinystalia yohimbe,
johimbi, yohimbehe, yohimbine)
Twinlab Yohimbe
Fuel, Nature's Purest
Herbal Niagara, KMax Power-for-Men
Pure Yohimbe Bark
Extract
Change in blood
pressure, heart
arrythmias,
respiratory
depression, heart
attack; deaths
reported.
None
60
Can their claims be trusted? Are they safe? Does FDA approve them?
Many of these questions come in the wake of the 1994 Dietary Supplement
Health and Education Act (DSHEA) which set up a new framework for FDA
regulation of dietary supplements.
DSHEA recognized that many people believe dietary supplements offer health
benefits and that consumers want a great opportunity to determine whether
supplements may help them. The law essentially gives dietary supplement
manufactures freedom to market more products as dietary supplements and provide
information about their products’ benefits eg, in product labeling.
But in choosing whether to use dietary supplements, FDA answers consumers’
question by noting that under DSHEA, FDA’s requirement for premarket review of
dietary supplements is less than that over other products it regulates, such as drugs
and many additives used in conventional foods.
This means that consumers and manufactures have responsibility for checking
the safety of dietary supplements and determining the truthfulness of label claims.
Anatomy of the New Requirements for Dietary Supplement Labels:
 Statement of identity (e.g. Ginseng)
 Net quantity of contents (e.g. 60 capsules)
 Structure-function claim and statement. This has not been evaluated by FDA. This
product is not intended to diagnose, treat, cure, or prevent any disease.
 Directions fir use (e.g. Take one capsule daily.)
 Supplement Facts panel (lists serving size, amount, and active ingredient)
 Other ingredients in descending order of predominance and by common name or
proprietary blend.
 Name and place of business of manufacturer, packer or distributor. This is the
address to write for more product information.
One thing dietary supplements are not is drugs. A drug, which sometimes can
be derived from plants used as traditional medicines, is an article that, among other
things, is intended to diagnose, cure, mitigate, treat, or prevent diseases. Before
marketing, drugs must undergo clinical studies to determine their effectiveness,
safety, possible interactions with other substances, and appropriate dosages, and FDA
must review these data and authorize the drugs' use before they are marketed. FDA
does not authorize or test dietary supplements.
A product sold as a dietary supplement and touted in its labeling as a new
treatment or cure for a specific disease or condition would be considered an
unauthorized--and thus illegal--drug. Labeling changes consistent with the provisions
in DSHEA would be required to maintain the product's status as a dietary supplement.
61
Another thing dietary supplements are not are replacements for conventional
diets, nutritionists say. Supplements do not provide all the known--and perhaps
unknown--nutritional benefits of conventional food.
Monitoring for Safety
As with food, federal law requires manufacturers of dietary supplements to
ensure that the products they put on the market are safe. But supplement
manufacturers do not have to provide information to FDA to get a product on the
market, unlike the food additive process often required of new food ingredients. FDA
review and approval of supplement ingredients and products is not required before
marketing.
Food additives not generally recognized as safe must undergo FDA's
premarket approval process for new food ingredients. This requires manufacturers to
conduct safety studies and submit the results to FDA for review before the ingredient
can be used in marketed products. Based on its review, FDA either authorizes or
rejects the food additive.
In contrast, dietary supplement manufacturers that wish to market a new
ingredient (that is, an ingredient not marketed in the United States before 1994) have
two options. The first involves submitting to FDA, at least 75 days before the product
is expected to go on the market, information that supports their conclusion that a new
ingredient can reasonably be expected to be safe. Safe means that the new ingredient
does not present a significant or unreasonable risk of illness or injury under conditions
of use recommended in the product's labeling.
The information the manufacturer submits becomes publicly available 90 days
after FDA receives it.
Another option for manufacturers is to petition FDA, asking the agency to
establish the conditions under which the new dietary ingredient would reasonably be
expected to be safe. To date, FDA's Center for Food Safety and Applied Nutrition has
received no such petitions.
Under DSHEA, once a dietary supplement is marketed, FDA has the
responsibility for showing that a dietary supplement is unsafe before it can take action
to restrict the product's use. This was the case when, in June 1997, FDA proposed,
among other things, to limit the amount of ephedrine alkaloids in dietary supplements
(marketed as ephedra, Ma huang, Chinese ephedra, and epitonin, for example) and
provide warnings to consumers about hazards associated with use of dietary
supplements containing the ingredients. The hazards ranged from nervousness,
dizziness, and changes in blood pressure and heart rate to chest pain, heart attack,
hepatitis, stroke, seizures, psychosis, and death. The proposal stemmed from FDA's
review of adverse event reports it had received, scientific literature, and public
comments. FDA has received many comments on the 1997 proposal.
Also in 1997, FDA identified contamination of the herbal ingredient plantain
with the harmful herb Digitalis lanata after receiving a report of a complete heart
block in a young woman. FDA traced all use of the contaminated ingredient and
asked manufacturers and retailers to withdraw these products from the market.
62
DSHEA also gives FDA authority to establish good manufacturing practices,
or GMPs, for dietary supplements. In a February 1997 advance notice of proposed
rulemaking, the agency said it would establish dietary supplement GMPs if, after
public comment, it determined that GMPs for conventional food are not adequate to
cover dietary supplements, as well. GMPs, the agency said, would ensure that dietary
supplements are made under conditions that would result in safe and properly labeled
products.
Besides FDA, individual states can take steps to restrict or stop the sale of
potentially harmful dietary supplements within their jurisdictions. For example,
Florida has banned some ephedra-containing products, and other states have said they
are considering similar action.
Also, the industry strives to regulate itself, the Council for Responsible
Nutrition's Cordaro says. He cites the GMPs that his trade group and others developed
for their member companies. FDA is reviewing these GMPs as it considers whether to
pursue mandatory industry-wide GMPs. Another example of self-regulation, Cordaro
says, is the voluntary use of a warning about ephedra products that his organization
drafted. He says that about 90 percent of U.S. manufacturers of products containing
ephedra alkaloids now use this warning label.
Understanding Claims
Claims that tout a supplement's healthful benefits have always been a
controversial feature of dietary supplements. Manufacturers often rely on them to sell
their products. But consumers often wonder whether they can trust them.
Under DSHEA and previous food labeling laws, supplement manufacturers
are allowed to use, when appropriate, three types of claims: nutrient-content claims,
disease claims, and nutrition support claims, which include "structure-function
claims."
Nutrient-content claims describe the level of a nutrient in a food or dietary
supplement. For example, a supplement containing at least 200 milligrams of calcium
per serving could carry the claim "high in calcium." A supplement with at least 12 mg
per serving of vitamin C could state on its label, "Excellent source of vitamin C."
Disease claims show a link between a food or substance and a disease or healthrelated condition. FDA authorizes these claims based on a review of the scientific
evidence. Or, after the agency is notified, the claims may be based on an authoritative
statement from certain scientific bodies, such as the National Academy of Sciences,
that shows or describes a well-established diet-to-health link. As of this writing,
certain dietary supplements may be eligible to carry disease claims, such as claims
that show a link between:

the vitamin folic acid and a decreased risk of neural tube defect-affected
pregnancy, if the supplement contains sufficient amounts of folic acid

calcium and a lower risk of osteoporosis, if the supplement contains sufficient
amounts of calcium

psyllium seed husk (as part of a diet low in cholesterol and saturated fat) and
coronary heart disease, if the supplement contains sufficient amounts of
psyllium seed husk.
63
Nutrition support claims can describe a link between a nutrient and the deficiency
disease that can result if the nutrient is lacking in the diet. For example, the label of a
vitamin C supplement could state that vitamin C prevents scurvy. When these types of
claims are used, the label must mention the prevalence of the nutrient-deficiency
disease in the United States.
These claims also can refer to the supplement's effect on the body's structure or
function, including its overall effect on a person's well-being. These are known as
structure-function claims.
Examples of structure-function claims are:

Calcium builds strong bones.

Antioxidants maintain cell integrity.

Fiber maintains bowel regularity.
Manufacturers can use structure-function claims without FDA authorization. They
base their claims on their review and interpretation of the scientific literature. Like all
label claims, structure-function claims must be true and not misleading.
Structure-function claims can be easy to spot because, on the label, they must be
accompanied with the disclaimer "This statement has not been evaluated by the Food
and Drug Administration. This product is not intended to diagnose, treat, cure, or
prevent any disease."
Manufacturers who plan to use a structure-function claim on a particular product
must inform FDA of the use of the claim no later than 30 days after the product is first
marketed. While the manufacturer must be able to substantiate its claim, it does not
have to share the substantiation with FDA or make it publicly available.
If the submitted claims promote the products as drugs instead of supplements,
FDA can advise the manufacturer to change or delete the claim.
Because there often is a fine line between disease claims and structure-function
claims, FDA in April 1998 proposed regulations that would establish criteria under
which a label claim would or would not qualify as a disease claim. Among label
factors FDA proposed for consideration are:

the naming of a specific disease or class of diseases

the use of scientific or lay terminology to describe the product's effect on one
or more signs or symptoms recognized by health-care professionals and
consumers as characteristic of a specific disease or a number of different
specific diseases

product name

statements about product formulation

citations or references that refer to disease

use of the words "disease" or "diseased"
64

art, such as symbols and pictures

statements that the product can substitute for an approved therapy (for
example, a drug).
FDA's proposal is consistent with the guidance on the distinction between
structure-function and disease claims provided in the 1997 report by the President's
Commission on Dietary Supplement Labels.
If shoppers find dietary supplements whose labels state or imply that the product
can help diagnose, treat, cure, or prevent a disease (for example, "cures cancer" or
"treats arthritis"), they should realize that the product is being marketed illegally as a
drug and as such has not been evaluated for safety or effectiveness.
FTC regulates claims made in the advertising of dietary supplements, and in
recent years, that agency has taken a number of enforcement actions against
companies whose advertisements contained false and misleading information. The
actions targeted, for example, erroneous claims that chromium picolinate was a
treatment for weight loss and high blood cholesterol. An action in 1997 targeted for
an ephedrine alkaloid supplement because they understated the degree of the product's
risk and featured a man falsely described as a doctor.
Fraudulent Products
Consumers need to be on the lookout for fraudulent products. These are products
that don't do what they say they can or don't contain what they say they contain. At
the very least, they waste consumers' money, and they may cause physical harm.
Fraudulent products often can be identified by the types of claims made in their
labeling, advertising and promotional literature. Some possible indicators of fraud,
says Stephen Barrett, M.D., a board member of the National Council Against Health
Fraud, are:

Claims that the product is a secret cure and use of such terms as
"breakthrough," "magical," "miracle cure," and "new discovery." If the
product were a cure for a serious disease, it would be widely reported in the
media and used by health-care professionals.

"Pseudomedical" jargon, such as "detoxify," "purify" and "energize" to
describe a product's effects. These claims are vague and hard to measure,
Barrett says. So, they make it easier for success to be claimed "even though
nothing has actually been accomplished," he says.

Claims that the product can cure a wide range of unrelated diseases. No
product can do that, he says.

Claims that a product is backed by scientific studies, but with no list of
references or references that are inadequate. For instance, if a list of references
is provided, the citations cannot be traced, or if they are traceable, the studies
are out-of-date, irrelevant, or poorly designed.

Claims that the supplement has only benefits--and no side effects. A product
"potent enough to help people will be potent enough to cause side effects,"
Barrett says.
65

Accusations that the medical profession, drug companies and the government
are suppressing information about a particular treatment. It would be illogical,
Barrett says, for large numbers of people to withhold information about
potential medical therapies when they or their families and friends might one
day benefit from them.
Though often more difficult to do, consumers also can protect themselves from
economic fraud, a practice in which the manufacturer substitutes part or all of a
product with an inferior, cheaper ingredient and then passes off the fake product as
the real thing but at a lower cost. Varro Tyler, Ph.D., Sc. D., a distinguished professor
emeritus of pharmacognosy (the study of medicinal products in their crude, or
unprepared, form) at Purdue University in West LaFayette, Ind., advises consumers to
avoid products sold for considerably less money than competing brands. "If it's too
cheap, the product is probably not what it's supposed to be," he says.
Quality Products
Poor manufacturing practices are not unique to dietary supplements, but the
growing market for supplements in a less restrictive regulatory environment creates
the potential for supplements to be prone to quality-control problems. For example,
FDA has identified several problems where some manufacturers were buying herbs,
plants and other ingredients without first adequately testing them to determine
whether the product they ordered was actually what they received or whether the
ingredients were free from contaminants.
To help protect themselves, consumers should:

Look for ingredients in products with the U.S.P. notation, which indicates the
manufacturer followed standards established by the U.S. Pharmacopoeia.

Realize that the label term "natural" doesn't guarantee that a product is safe.
"Think of poisonous mushrooms," says Elizabeth Yetley, Ph.D., director of
FDA's Office of Special Nutritionals. "They're natural."

Consider the name of the manufacturer or distributor. Supplements made by a
nationally known food and drug manufacturer, for example, have likely been
made under tight controls because these companies already have in place
manufacturing standards for their other products.

Write to the supplement manufacturer for more information. Ask the company
about the conditions under which its products were made.
Purity and Standardization
Several International Organizations have voiced to do work on herbs in the
light of light modern knowledge. The World Health Organization (WHO) is now
active in promoting the traditional medicines and the herbal treatment. The
Committee on Safety of Medicines encourages community and hospital pharmacists
to submit yellow card scheme reports for all herbal products. According to USP, a
drug product is described as stable if it maintains the following elements of stability:
physical, chemical, microbial, toxicological and therapeutic forms of stability.
66
No doubt some individual herbal extracts have been tested for their quality,
activity and toxicity but less effort are made to explore the finished herbal drug
formulations for their possible toxicity and stability over the defined shelf life
assigned to them by the manufacturers.
Standardized phytopharmaceuticals must have a known content of active or
characteristic substances. Exogenous substances must be below specified limits
recommended by regulatory agencies. Depending on the type of preparation,
organoleptic features, moisture and ash content, physical properties and adulterants
are checked to confirm identity and determine purity. Microbiological contamination
and foreign materials are important quality criteria in the testing of medicinal plants.
Other areas of concern are the purity and standardization of supplements.
Supplements, unlike drugs, are not regulated to ensure that they are pure or that they
contain the ingredients or the amount of active ingredient they claim to contain. As a
result, the supplement may not be pure. Or, the amount of active ingredient in a dose
of a supplement may vary, especially when whole herbs are ground or made into
extracts to produce a tablet, capsule, or solution. The buyer is at risk of getting less,
more, or, in some cases, none of the active ingredient in a supplement.
Standardization requires that each individual dosage form of the product contain a
precise amount of its active ingredient or ingredients. However, most herbal products
are mixtures of several substances, and which ingredient is the most active is not
always known. Therefore, determining which ingredient or ingredients should be
considered active and thus would be subject to standardization can be difficult. Some
supplements have been standardized and may include a designation of standardization
on the label.
Advice on how to choose a pure, standardized product varies from expert to
expert. Most experts recommend buying from a well-known manufacturer, and many
recommend buying products made in Germany, because oversight of supplements is
stricter there than in the United States.
Reading and Reporting
Consumers who use dietary supplements should always read product labels,
follow directions, and heed all warnings.
Supplement users who suffer a serious harmful effect or illness that they think
is related to supplement use should call a doctor or other health-care provider. He or
she in turn can report it to FDA (www.fda.gov/medwatch/report/hcp.htm on the
MedWatch Website).
Consumers also may call the toll-free MedWatch number or go to
www.fda.gov/medwatch/report/consumer/consumer.htm on the MedWatch Website to
report an adverse reaction. To file a report, consumers will be asked to provide:

name, address and telephone number of the person who became ill

name and address of the doctor or hospital providing medical treatment

description of the problem

name of the product and store where it was bought.
67
Consumers also should report the problem to the manufacturer or distributor listed
on the product's label and to the store where the product was bought.
Today's Dietary Supplements
The report of the President's Commission on Dietary Supplement Labels,
released in November 1997, provides a look at the future of dietary supplements. It
encourages researchers to find out whether consumers want and can use the
information allowed in dietary supplement labeling under DSHEA. It encourages
studies to identify more clearly the relationships between dietary supplements and
health maintenance and disease prevention. It urges FDA to take enforcement action
when questions about a product's safety arise. And it suggests that FDA and the
industry work together to develop guidelines on the use of warning statements on
dietary supplement labels.
FDA generally concurred with the commission's recommendations in the
agency's 1998 proposed rule on dietary supplement claims.
While much remains unknown about many dietary supplements--their health
benefits and potential risks, for example--there's one thing consumers can count on:
The availability of a wide range of such products. But consumers who decide to take
advantage of the expanding market should do so with care, making sure they have the
necessary information and consulting with their doctors and other health professionals
as needed.
"The majority of supplement manufacturers are responsible and careful, but,
as with all products on the market, consumers need to be discriminating. FDA and
industry have important roles to play, but consumers must take responsibility, too."
Conclusion and recommendations (140-142)
FDA regulates dietary supplements under a different set of regulations than
those covering "conventional" foods and drug products (prescription and Over-theCounter). Under the Dietary Supplement Health and Education Act of 1994
(DSHEA), the dietary supplement manufacturer is responsible for ensuring that a
dietary supplement is safe before it is marketed. FDA is responsible for taking action
against any unsafe dietary supplement product after it reaches the market. Generally,
manufacturers do not need to register with FDA nor get FDA approval before
producing or selling dietary supplements. Manufacturers must make sure that product
label information is truthful and not misleading.
FDA's post-marketing responsibilities include monitoring safety, e.g.
voluntary dietary supplement adverse event reporting, and product information, such
as labelling, claims, package inserts, and accompanying literature. The Federal Trade
Commission regulates dietary supplement advertising.
Conversely, trying to balance the body's biochemistry with mineral and
vitamin supplements is very difficult because of the dynamic complexity of the
human organism; the daily diet; exposure to environmental poisons; stress factors;
genetics, etc. If your patient needs minerals, you use a whole-food complex
supplement containing a multitude of plant foods known to be mineral-rich, and also
68
include synergistic vitamins; amino acids; trace mineral activators; and enzymes. You
have found that nature's design is a safer choice due its inherent intelligence in
providing a variety of nutrients, synergists and low dosages. When using whole-food
supplements, doctors must realize a shift and the need to stop regarding foods as
chemicals. We have to give up the line of thinking and grasp the holistic perspective,
understanding that the "more is better" attitude does not apply to food; vitamins;
minerals; or amino acids. The quality of the food complex becomes more important
than the quantity of individual vitamins, minerals or amino acids.
As with all supplements, buyer should be aware. If you don't read and
understand what's on a supplement label, then you may be contradicting yourself to
your patients. The truth is that many companies tout their products as whole foods
when they're offering mixtures of foods along with isolates. And some so-called
"whole-food" supplements are not grown in soil, under natural, traditional farming
conditions. The way to tell the difference is rather simple: A whole food is just that - a
food like a carrot, beet, celery or potato flour, for instance. Isolates are stated on the
label by their chemical names, such as vitamin A palmitate; mixed tocopherols;
ascorbic acid; pyridoxine; niacin; niacinamide; etc.
Physicians should ask their patients about their use of herbal products and
advise patients with substance use disorders to avoid herbs with abuse potential, such
as ma huang and kava. Herbs carry the risk of side effects, just like other medications
possible. Pregnant and nursing women should be advised to avoid herbal products that
have not been adequately tested, and patients should be made aware that the FDA
provides little oversight of these products. Therapeutic doses have not been
established, and indications for the use of herbs have not been approved.
Psychoactive herbs have been popular for centuries. Some patients prefer the
alternative medicine option. Physicians who understand and respect herbal
therapeutics are more likely to help like-minded patients make safe choices.
Physicians should be aware of the possible benefits of herbal remedies, while paying
attention to their risks. There is still much to learn about the efficacy and toxicity of
herbal products. As more Americans turn to medicinal herbs, physicians must educate
themselves about this new class of drugs.
A vitamin is like an enzyme or catalyst. It assists in a chemical reaction. By
themselves, they will help prevent a nutritional deficiency and in persons on very low
calorie diets (less than 1200 calories per day), vitamin supplements provide missing
nutrients. Vitamins though are not enough. You need protein, fat and carbohydrate to
build and maintain the human body. If you focus on eating a variety of foods, your
requirements of vitamins and minerals will probably be met. Unless your doctor has
recommended a specific vitamin for a health problem you have, you may be wasting
your money on supplements.
Food supplements in Egypt (143)
According to the Egyptian Ministry of Health’s regulations, natural products,
vitamins and food supplements are prohibited from importation into Egypt in their
finished forms. The only way this can be marketed in Egypt is by local manufacturing
under license, or by sending ingredients and premixes to a local pharmaceutical firm
to be prepared and packed here in accordance with specifications of the Ministry of
69
Health. Otherwise, only local factories have the right to produce and supplements, and
import raw materials to be used in the manufacturing process.
70
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