Risk Factors in Glutathione Depletion
Glutathione, a nutrient-like substance that is made in the body as well as consumed
through the diet, is one of the most important protective molecules in human biology. As
a powerful antioxidant it neutralizes harmful free radicals and recycles vitamins E and C,
the other two main dietary antioxidants. As an anticarcinogen it binds with and
eliminates cancer-causing chemicals. In these roles it acts as a molecular “garbage
collector,” cruising all tissues and removing unwanted toxins.
Another important role of glutathione is to provide the body with amino acids for the vital
protein functions of cells. In this role too it can affect every cell and tissue in the body.
Interestingly, the breakdown of glutathione into its three amino acids is a reversible
process; the entire glutathione pool throughout the body turns over daily as it is both
broken down and synthesized. Large stores of glutathione are not maintained, so it
must be replenished daily.
How much glutathione is needed?
An official recommended intake has not been set for glutathione because diet is not the
sole source, and therefore, glutathione cannot be classified as an essential nutrient.
Scientists have measured the amount of glutathione provided by foods and found that
the best sources are fresh fruits and vegetables and freshly prepared meats. Diets that
are high in these foods provide approximately 150 milligrams of glutathione per day,
whereas poor diets may provide as little as 3 milligrams daily of glutathione.
In general, scientific evidence suggests that a healthy intake should be in the range of
100 to 150 milligrams per day. However, the average intake in the U.S. is only about 35
milligrams per day, leaving a considerable gap.
Considering the variety of factors that can deplete glutathione, a sizable proportion of the
population could conceivably benefit from increasing its glutathione intake, either by
eating more fresh foods or by supplementing their diet.
Risk factor: morning
Researchers have recently discovered that the glutathione cycle follows a diurnal
pattern, with lowest levels occurring in the morning. Levels increase in a spiked pattern
about six hours after each meal and peak between 2:00 and 3:30 in the morning,
followed by a steep decline.1

This cycle results in a relative deficiency of glutathione in the morning hours that may
extend into the afternoon. In people over age 60, there is a more pronounced difference
between the glutathione peaks and valleys, which could be important given that the
glutathione “valleys” are periods of vulnerability for oxidative stress and age-related
chronic conditions.
Risk factor: age
Glutathione status generally begins to weaken around age 45 and declines precipitously
after age 60.2
The aging body is not able to make as much glutathione due to
decreased enzyme activity and lower efficiency of the cellular signals that trigger
glutathione synthesis.
This loss in glutathione protection may leave one more vulnerable to oxidative processes
that underlie chronic diseases of aging such as heart disease, cancer and age-related
eye disease. Scientific research has correlated reduced glutathione status and/or
dietary intakes with early markers of cardiovascular disease;3 higher risk of oral and
pharyngeal cancer,4,5 and age-related macular degeneration.6,7

In one study, higher glutathione status in older individuals was correlated with good
health as assessed by multiple measures: fewer number of illnesses, higher levels of
self-rated health, lower cholesterol, lower body mass index and lower blood pressures.
In contrast, those with poorer health as well as those diagnosed with arthritis, diabetes
or heart disease had lower glutathione levels. 8

Another study of 87 healthy women aged 60 to 103 years found that high blood
glutathione concentrations were characteristic of long-lived women who were in
excellent physical and mental health.9

Risk factor: diet
Since fresh foods are truly the only good sources of glutathione, a Mediterranean-style
diet that is plentiful in fresh fruits and vegetables and freshly prepared meats is best for
maintaining good glutathione status. However, many diets today rely heavily on
processed foods. These do not provide glutathione since most methods of food
processing destroy it. Likewise, grain and dairy products are not good sources.
Therefore, many diets commonly consumed in the U.S. provide inadequate glutathione
to support optimal health.
Risk factors: lifestyle habits
Lifestyle habits such as cigarette smoking and excessive consumption of alcohol are
detrimental to glutathione status because they dramatically increase the demand for
protection. High levels of glutathione are normally maintained in the fluid lining of the
lungs (alveolar fluid) in order to detoxify and neutralize harmful inhaled compounds.
Glutathione is extensively oxidized in smokers as compared to nonsmokers.10
Alcohol independently makes the lungs more susceptible to oxidative injury, and the
damage is compounded in people who both smoke and drink. Acute respiratory distress
syndrome has been linked in the past with a history of alcohol abuse. Recent studies
suggest this may be due to depletion of the glutathione levels within the alveolar space
by alcohol by as much as 80 to 90 percent.11 In those who not only drink excessively but
also smoke, glutathione defenses are completely overwhelmed.12
Risk factor: obesity
Obesity is correlated with oxidative stress stemming from metabolic processes that
create a low-level inflammation in white adipose tissue (fat stores). This chronic
oxidative stress is believed to be a major contributing factor to the development of insulin
resistance, impaired glucose tolerance and diabetes. Antioxidant defenses including
glutathione are depleted in obese persons.13,14,15
Risk factor: diabetes
The hyperglycemia that characterizes diabetes causes metabolic changes that speed
the production of damaging free radicals, and oxidative stress is believed to play an
important role in the development of diabetes complications such as kidney damage,
nerve damage and blindness. Glutathione levels are low in people with diabetes as
compared to non-diabetic controls.16 In an animal model of diabetes, dietary glutathione
can suppress oxidative stress, particularly in the lens of the eye.17
Other risk factors
Any condition that increases the oxidative load on the body is by definition one that uses
more glutathione, potentially increasing requirements beyond what is furnished in the
diet or what the body is able to produce. Oxidative stress is linked to a host of diseases
and disorders that are common today, including cardiovascular disease and stroke,
cancer, neurodegenerative diseases such as Parkinson’s and Alzheimer’s, diabetes,
cataracts, macular degeneration, HIV, hepatitis B, asthma, chronic obstructive
pulmonary disease and other lung diseases, and inflammatory disorders. In fact,
oxidative stress has been linked to more than 250 diseases, all of which translate to
increased challenges for glutathione and other components of the body’s antioxidant
defense system.
Beyond tobacco and alcohol, there are other sources of oxidants in our environment
such as ultraviolet radiation, ionizing radiation, oil fumes, saturated fats, pollutants and
chemicals. There is no reliable way to calculate cumulative exposure to reactive
oxidants or to establish a precise requirement for glutathione for all people. However, it
is possible to calculate the number of people with known exposures, giving an idea of
the magnitude of the “glutathione gap” in the U.S. today.
The following chart provides estimates of the number of Americans who have known risk
factors for glutathione depletion and could potentially benefit from increasing their
glutathione intake

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