Antioxidant Micronutrients 9.1 Antioxidants

30 Pages·2017·1.87 MB·English

Chapter 9: Antioxidant Micronutrients

This chapter will describe what antioxidants are and then discuss the three major antioxidant
micronutrients: vitamin E, vitamin C and selenium.

• 9.1 Antioxidants
• 9.2 Vitamin E
• 9.3 Vitamin C
• 9.4 Selenium

9.1 Antioxidants

The antioxidant vitamins and minerals include the following:
• Vitamin E
• Vitamin C
• Selenium
• Iron
• Copper
• Zinc
• Manganese
• Riboflavin

In this section, we are going to cover vitamin E, vitamin C, and selenium in detail because being
an antioxidant is their primary function.

Subsections:
• 9.11 Free Radicals & Oxidative Stress
• 9.12 What is an Antioxidant?
• 9.13 Meaningful Antioxidant(s)
• 9.14 Too Much of a Good Thing? Antioxidants as Pro-oxidants
9.11 Free Radicals & Oxidative Stress

Before you can understand what an antioxidant is, it is important to have an understanding of
oxidants. As you have learned already, oxidation is the loss of an electron as shown in Figure
9.111.

Figure 9.111 The purple compound is oxidized; the orange compound is reduced1

Some important terms to understand:

Free Radical - a molecule with an unpaired electron in its outer orbital.

The following example shows normal oxygen losing an electron from its outer orbital and thus,
becoming an oxygen free radical.

Figure 9.112 Normal oxygen is converted to an oxygen free radical by losing one electron in its
outer orbital, leaving one unpaired electron.
Free radicals are highly reactive because they actively seek an electron to stabilize (pair with)
the unpaired electron within the molecule.

Reactive Oxygen Species (ROS) - an oxygen-containing, free radical species.

Some of the most common ROS are (● symbolizes radical):
• Superoxide (O ●)
2
• Hydroxyl Radical (●OH)
• Hydrogen Peroxide Radical (HO ●)
2
• Peroxyl Radical (ROO ●)
2
• Alkoxyl Radical (RO●)
• Ozone (O )
3
• Singlet Oxygen (1O )
2
• Hydrogen Peroxide (H O )
2 2

Oxidative Stress - the imbalance between the production of ROS/free radicals and the body’s
ability to quench them.

Free radicals can be generated by a variety of sources that can be classified as endogenous
(within the body) and exogenous sources (outside the body). The link below is a figure that
shows how ROS can be generated from each of these sources.
The Required Web Link below does a good job explaining what oxidative stress is, how free
radicals can be formed, how they are neutralized by antioxidants, where we get antioxidants.

Required Web Link
What is Oxidative Stress, Free Radicals & Antioxidants

Figure 9.113 shows that inflammation caused by hitting your thumb with a hammer, exposure
to UV light, radiation, smoking, and air pollution are all sources of free radicals.
Figure 9.113 Some sources of free radicals

So, we have these free radicals searching for an electron, what's the big deal? The problem
arises if the free radicals oxidize LDLs, proteins, or DNA as shown below.

Figure 9.114 Free radicals can attack LDLs, proteins, and DNA2,3

Oxidized LDL is more likely to contribute to atherosclerosis (hardening of the arteries) than
normal LDL. Protein oxidation is believed to be involved in the development of cataracts.
Cataracts are the clouding of the lens of the eye. If nucleotides within DNA are oxidized, it can
result in a mutation. A mutation is a change in the nucleotide or base pair sequence of DNA.
Mutations are a common occurrence in cancer.
References & Links
1. http://en.wikipedia.org/wiki/Image:Gulf_Offshore_Platform.jpg

Links
What is Oxidative Stress, Free Radicals & Antioxidants -
https://www.youtube.com/watch?v=9OgCjhAFCC0
Cataract Vision Simulator - https://www.aao.org/eye-health/diseases/cataracts-vision-
simulator

9.12 What is an Antioxidant?

We are now ready to move on to antioxidants, which as their name indicates, combat free
radicals, ROS, and oxidative stress. As a humorous introduction, the link below is to a cartoon
that shows Auntie Oxidant kicking free radicals out of the bloodstream.

Required Web Link
Auntie Oxidant

Unfortunately, it's not quite that simple. You have probably heard the saying "take one for the
team." Instead of taking one for the team, antioxidants "give one for the team." The ‘giving’ in
this example is the donation of an electron from itself to a free radical, in order to regenerate a
stable compound, as shown in Figure 9.121.

Figure 9.121 Regeneration of normal oxygen from oxygen free radical by the donation of an
electron from an antioxidant
Donating an electron is how vitamins (A, C & E) act as antioxidants. Minerals, on the other
hand, are not antioxidants themselves. Instead, they are cofactors for antioxidant enzymes.

These antioxidant enzymes include:

1. Superoxide dismutase (SOD): uses copper, zinc, and manganese as cofactors (there is
more than one SOD enzyme); converts superoxide to hydrogen peroxide and oxygen1.

2. Catalase: uses iron as a cofactor; converts hydrogen peroxide to water1.

3. Glutathione peroxidase (GPX): is a selenoenzyme that converts hydrogen peroxide to
water. It can also convert other reactive oxygen species (ROSs) to water1.

4. alpha-Lipoic acid: reacts with reactive oxygen species such as superoxide radicals,
hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also
protects membranes by interacting with vitamin C, which may in turn recycle vitamin E3.

5. Peroxiredoxin: participates directly in eliminating hydrogen peroxide (H O ) and
2 2
neutralizing other reactive oxygen species (ROS)4.

The actions of some of these enzymes is shown in Figure 9.122.

Figure 9.122 Antioxidant enzymes that use minerals as cofactors

Antioxidants are thought to work in concert with one another, forming what is known as the
antioxidant network. For example, vitamin E, vitamin C, and selenium often work together to
process a single ROS as shown in Figure 9.123. (You do not have to memorize the intermediates
right now, but as you get through the various subsections, they should start to make sense)
Notice how the Vitamin E Cycle processes the ROS (reaction on the bottom left,) and then
works with the Vitamin C Cycle, and finally the Selenium Cycle to eliminate the intermediate
chemicals.

Figure 9.123 An example of an antioxidant network2

References & Links
1. Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont,
CA: Wadsworth Publishing.
2. Packer L, Weber SU, Rimbach G. (2001) Molecular aspects of alpha-tocotrienol antioxidant
action and cell signalling. J Nutr 131(2): 369S-373S.
3. Packer L, Witt EH, Tritschler HJ. (1995) alpha-Lipoic acid as a biological antioxidant. Free Radic
Biol Med. 19(2):227-50.
4. Yuan J, Murrell GA, Trickett A, Landtmeters M, Knoops B, Wang MX. (2004) Overexpression
of antioxidant enzyme peroxiredoxin 5 protects human tendon cells against apoptosis and loss
of cellular function during oxidative stress. Biochim Biophys Acta. 1693(1):37-45.

Link
Auntie Oxidant - http://www.ibiblio.org/Dave/Dr-Fun/df200005/df20000523.jpg
9.13 Meaningful Antioxidant(s)

There is a lot of confusion among the public on antioxidants. For the most part, this is for a
good reason. Many food companies put antioxidant numbers on the packages that sound good
to consumers, who often have no idea how to interpret them. Thus, it is increasingly important
to have an understanding of what a meaningful antioxidant actually is.

A meaningful antioxidant has two characteristics (these are based on the assumption that the
compound is an antioxidant):

1. Found in appreciable amounts in a location where there are free radicals/ROS that need
to be quenched
2. It is not redundant with another antioxidant that is already providing that function

What do these mean? Let's consider the example of lycopene and vitamin E (alpha-tocopherol),
which are both fat-soluble antioxidants. In a lab setting (in vitro), lycopene has been shown to
be 10x more effective in quenching singlet oxygen than alpha-tocopherol1. However, when you
look at the concentrations found in the body, there is far more alpha-tocopherol than lycopene
as shown below:
• LDL – 13x more alpha-tocopherol than lycopene1.
• Prostate – 162x higher alpha-tocopherol than lycopene concentrations
• Skin – 17 to 269x higher alpha-tocopherol than lycopene concentrations
• Plasma – 53x higher alpha-tocopherol than lycopene concentrations1
Thus, despite the fact that lycopene is a better antioxidant in vitro, alpha-tocopherol is likely
the more meaningful antioxidant in the body as evidenced by the fact that its concentration so
much higher in the various tissues (locations of need.) In addition, if lycopene and alpha-
tocopherol had similar antioxidant functions, lycopene’s potential antioxidant action is
redundant to alpha-tocopherol’s antioxidant function and thus, is less likely to be a meaningful
antioxidant.

References & Links
1. Erdman, J.W., Ford, N.A., Lindshield, B.L. Are the health attributes of lycopene related to its
antioxidant function? Arch Biochem Biophys, 483: 229-235, 2009.
9.14 Too Much of a Good Thing? Antioxidants as Pro-oxidants

A clinical trial once found that high-dose beta-carotene supplementation increased lung cancer
risk in smokers2. This is an example of findings that support that high doses of antioxidants may
be “too much of a good thing”, causing more harm than benefit. The parabolic, or U-shaped
figure, below displays how the level of nutrient concentration or intake (horizontal axis) relates
to an antioxidant measure (vertical axis). The lowest level of antioxidant intake or tissue
concentration results in nutrient deficiency if the antioxidant is essential (vitamins and
minerals). Intake levels above deficient, but less than optimal, are referred to as low
suboptimal. Suboptimal means the levels are not optimal. Thus, low suboptimal and high
suboptimal sandwich optimal. The high suboptimal level is between optimal and where the
nutrient becomes toxic.

Figure 9.142 How the levels of nutrient concentration or intake alters antioxidant measures in
the body. Adapted from reference 1

Another example of this phenomenon can be seen when we look at DNA damage in the
prostate gland of dogs as it relates to toenail selenium concentration measurements, which are
a good indicator of long-term selenium status1. Researchers found that when they plotted
prostate DNA damage (antioxidant measure) against toenail selenium status (nutrient
concentration or intake) that it resulted in a U-shaped curve like the one shown above1. Thus, it
is good to have antioxidants in your diet, but too much can be counterproductive.

References & Links
1. Waters DJ, Shen S, Glickman LT, Cooley DM, Bostwick DG, et al. (2005) Prostate cancer risk
and DNA damage: Translational significance of selenium supplementation in a canine model.
Carcinogenesis 26(7): 1256-1262.
2. Peto R, Doll R, Buckley JD, Sporn MB. Can dietary beta-carotene materially reduce human
cancer rates? Nature 290, 201-208, 1981.

9.2 Vitamin E

There are 8 different forms of vitamin E: 4 tocopherols and 4 tocotrienols. The difference
between tocopherols and tocotrienols is that the former have a saturated tail, while the latter
have an unsaturated tail. Within tocopherols and tocotrienols, the difference between the
different forms is the position of the methyl groups on the ring. The 4 different forms within the
tocopherol and tocotrienols are designated by the Greek letters: alpha, beta, gamma, and delta.
The difference in these structures is shown in the figures below. Notice the subtle differences
down the left-hand side of the various structures.

Figure 9.21 Structures of the different forms of vitamin E

For reasons that will be covered in a later subsection, the primary form of vitamin E found in
the body is alpha-tocopherol (the form discussed in Section 9.13.) The major, and possibly only,
function of vitamin E is as an antioxidant. When it serves as an antioxidant it forms an alpha-
tocopherol radical, as shown in Figure 9.23.