Anxiety, Stress & Depression

A supplement Approach
Anxiety and depression may arise from imbalances in neurotransmitters, such as
serotonin, norepinephrine, dopamine, GABA, and glutamate. Just as many prescription drugs are
hypothesized to treat anxiety or depression by restoring balance at a neurotransmitter level,
certain supplements may do the same. The amino acids tryptophan and 5-HTP are precursors to
serotonin, which in turn is a precursor to melatonin; the amino acids phenylalanine and tyrosine
are precursors to dopamine, which in turn is a precursor to norepinephrine. Thus, “targeted
amino acid therapy” with one or more of the above supplements may alleviate the symptoms of
depression and/or anxiety in some individuals. The amino acid taurine is a precursor to GABA,
an inhibitory neurotransmitter. The amino acid theanine is an antagonist to glutamate, an
excitatory neurotransmitter. One or both of these supplements may be beneficial in the treatment
of anxiety and/or depression. Norm Shealy, MD, PhD, a pioneer in holistic medicine, founder of
the American Holistic Medical Association in 1978, and author of many books, including Ninety
Days to Stress Free Living, reports that he has identified taurine deficiency in 88% of his patients
with depression.

There is no certain way of determining in advance whether a given individual might

benefit from 5-HTP, tyrosine, taurine, theanine, or a combination of these supplements.
Questionnaires such as included in the bestseller, The UltraMind Solution by Mark Hyman, MD
(2008) may help to guide treatment. Some practitioners find measurement of urine
neurotransmitter levels helpful as a guide to prescribing treatment – this test is readily available,
but the several hundred dollar cost may not be covered by health insurance. I personally am
skeptical of the value of this diagnostic test.

An alternative dietary supplement approach to targeted amino acid therapy is to take a

supplement which contains multiple amino acids in one supplement - these broad spectrum
amino acid supplements are referred to as 'free form amino acids,' and anecdotally, some
individuals with anxiety and/or depression experience symptom relief when they take such a
supplement. GenesaTM and Truehope® market free form amino acid supplements.
 The biochemical pathway by which 5-HTP is converted to serotonin and by which
tyrosine is converted to dopamine require vitamins and minerals (scientifically referred to as
coenzymes) to facilitate the enzymatic reactions – vitamins B6, B12, and folate as well as the
minerals magnesium and zinc are cofactors in these biochemical pathways. Thus,
supplementation with these vitamins and minerals may be beneficial in some individuals with
anxiety or depression. In a given individual, a genetic variation labeled a genetic polymorphism
might interfere with conversion of vitamin B6, B12, or folate into the active form that is used in
the body. Genetic testing for these polymorphisms (other than for folate) is not yet widely
available, is not covered by insurance, and is expensive. An empiric approach to treatment may
involve the administration of activated forms of these vitamins as a supplement. Methylfolate or
5-methyltetrahydrofolate, methylcobalamin, and pyridoxal 5’-phosphate are the activated forms
of folate, vitamin B12, and vitamin B6 respectively. There are several supplements on the market
which contain the activated forms of vitamin B6, vitamin B12, and folate in a single pill.

Stress may arise primarily from an underlying imbalance in neurotransmitters, or it may

arise from environmental factors (a stressful home life, financial difficulties, loss of a job,
inadequate sleep). The effects of stress on the body are mediated by the hypothalamus, a
structure in the brain; stress is often correlated with an imbalance in functioning of the adrenal
gland. In many individuals the condition labeled in holistic medicine as ‘adrenal fatigue’ is a
consequence of stress rather than a cause; it nonetheless may require treatment. Adaptogens by
definition are herbs which balance adrenal function. Rhodiola rosea is one of the best studied
herbs for anxiety and depression. Additional adaptogens include Cordycepys, Panax
ginseng, Eleutherococcus, and licorice, as well as a variety of other Ayurvedic herbs and
Traditional Chinese Medicine herbs. Many supplements contain a combination of adaptogens.
When stress arises from environmental factors, a variety of mind-body approaches that are
outside of the scope of this narrative may also be beneficial.

Anxiety, stress, and depression are often associated with inflammation and immune
system imbalance. Researchers are uncertain whether the inflammation and immune system
dysfunction are precursors to these conditions or a consequence. Either way, some individuals
with anxiety, stress, and depression feel better when taking supplemental fish oil. Fish oil
contains EPA and DHA (omega 3 fatty acids). EPA is an immediate biochemical precursor to
anti-inflammatory substances in the body named prostaglandins and leukotrienes. Flax contains
ALA, an omega 3 fatty acid which is a biochemical precursor to EPA and DHA. Thus flax is also
anti-inflammatory. However, the efficiency of the biochemical conversion of ALA to EPA and
then to DHA is poor – published reports indicate that on average, less than 20% of ALA is
converted to EPA, and as little as 5% of ALA is converted to DHA. Fish oil and flax (oil and
meal) readily oxidize (turn rancid) – it is advisable to prepare flax meal daily by grinding flax
seed, rather than purchasing flax meal, and to store keep fish oil in the refrigerator. Some experts
recommend against the use of flax oil based on a concern that even if packaged in a dark bottle
and refrigerated upon opening, the oil may turn rancid very quickly.

Vitamin D has anti-inflammatory and immune balancing actions in the body. Vitamin D is
not truly a vitamin; humans synthesize vitamin D in the skin from cholesterol when exposed to
ultraviolet B sunlight. Note that SPF 15 sunscreen blocks approximately 97% of the conversion
of cholesterol to vitamin D, and the rotation of the earth around the sun is such that in the
northern half of the United States, no UV-B rays of sunlight penetrate the ozone in the upper
atmosphere between mid October and mid April. Vitamin D status can be estimated by a blood
test, a 25-hydroxy vitamin D level, which is a standard test in conventional medicine. This
approximately $150 test may or may not be covered by health insurance. A 25 hydroxy vitamin
D level above 30 ng/ml (75 nmol/L) is considered a normal level. However, some individuals
with anxiety and depression subjectively report a dramatic improvement in symptoms only when
a vitamin D level greater than 50 ng/ml is achieved. The hypothesis to explain this observation is
that these individuals may have a genetic polymorphism of the vitamin D receptor, such that
vitamin D does not bind well to the receptor, and that this poor binding is overcome by achieving
higher levels of vitamin D. BEWARE that vitamin D is a fat soluble vitamin (as are vitamins A,
E, and K), and too much is toxic. As a general rule of thumb, an individual will not experience
toxicity unless the 25 hydroxy vitamin D level is greater than 100 ng/ml. The Institute of
Medicine reports 4000 IU daily as the "Upper Limit" of safe intake of supplemental vitamin D.

One of the tenets of holistic medicine is to strive to identify and treat the root cause of a
condition. Functional medicine is a holistic approach to treatment that guides the practitioner
(and the patient) in identifying and treating the root cause of a condition (for a narrative
description of functional medicine, go to Functional Medicine). In some individuals, anxiety
and depression seem to arise as a consequence of imbalance in the gastrointestinal tract, food
sensitivities, or bioaccumulation of environmental toxins, including heavy metals such as lead
and mercury. Books which address examples of situations in which anxiety and depression
seemingly arise from disturbances in GI function, food sensitivities, or environmental toxicity
include The UltraMind Solution by Mark Hyman, MD (2008) and Healing Depression & Bipolar
Disorder without Drugs by Gracelyn Guyol (2006). Some individuals with anxiety or depression
feel better when treated with supplements such as probiotics (beneficial bacteria), glutamine (an
amino acid), digestive enzymes, an allergy elimination diet, or a detoxification regimen.

In conclusion, the underlying cause of anxiety, stress and depression varies from person
to person. There are no simple answers. Treatment must be individualized, and often this
involves a trial and error approach.

Disclaimer: the preceding is intended as educational material and not as individual treatment
recommendations.

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