NFS284 Chapter 8, 9 – Vitamins
Too little and too much both increase harm.
We concentrate on "from food" because it reflects the quality of the diet. We do not worry too
much about the B vitamins (thiamin, niacin, riboflavin). Anything that is 10% or below means
that there is a low prevalence of adequate intake. For vitamin C in smokers, there is a high
prevalence of inadequate intake because smokers have a higher vitamin C requirement. This is
because vitamin C is an antioxidant vitamin (discussed later). If you smoke, you produce a lot of
free radicals in your lungs. Even among non-smokers, men have a slightly higher prevalence of
inadequate intake for vitamin C (e.g., do not consume as much fruits and vegetables, or
requirements for men is higher because they have larger bodies).
For women, there is a high prevalence of inadequate intake of folate. This is a problem for
women who are planning to get pregnant.
Iron, thiamin, riboflavin, and niacin are lost as a result of processing when we make white flour.
Folate is added to grain products because we found that there wasn't enough folate in our food
Hazel ends up being sicker than she intended because if you add up the amount of vitamin C, it
exceeds the UL by double the amount. If you have too much vitamin C, you don't absorb it, and
it ends up in your colon, which can make you feel nauseous. These gastrointestinal symptoms
resolve very quickly once you get the dose down, but in other cases, excessive intakes can be
You rarely exceed the UL just from food because food is self-limiting. There is only so much
that you can put into your stomach in any one time but it is easy to swallow multiple pills. Slide 8
Some nutrients are fairly insoluble and they go from one end to the other and we don't ever
absorb them. Other nutrients are very readily absorbed from our foods. The DRIs take into
account the fact that some nutrients are poorly absorbed, so the DRIs are set higher.
Fat-soluble vitamins can be stored in the liver and the adipose tissue.
The body recycles vitamin B12. Most organic vitamins and compounds get degraded and
excreted. Vitamin B12 is well conserved in the body.
Vitamins participate in enzyme function. Vitamins are chemically modified to form a coenzyme.
The vitamin consumed from food is not in the right form, so there is a chemical modification that
converts the vitamin into a form called a coenzyme. The coenzyme binds to a protein to make an
active enzyme. If you have certain vitamin deficiencies, some of these enzymes in your body
will not work. The functional enzyme-coenzyme complex catalyzes reactions. Many B vitamins
function as coenzymes in energy metabolism.
We talked about DNA methylation with respect to epigenetics. Single carbon metabolism is
involved in creating the methyl groups and transfering the methyl groups onto different
molecules in the body, including DNA. There is a link between these vitamins and epigenetic
Thiamine and niacin are historically important because they were among the first essential
nutrients that were discovered and helped to cure deficiency diseases. Thiamin, riboflavin, and
niacin are not nutrients that we have too much concern about. They are quite widespread in our
The kernel and the germ from a lot of grain products were removed because this tends to reduce
the spoilage of the rice. If you don't add back the nutrients that you removed, you end up with a
thiamine deficient product. They found out that thiamine was the missing nutrient in the
unenriched white rice. We enrich our food supply with thiamine. Any grain product that has been processed (e.g.,
wheat) will be enriched to bring the thiamine levels back up to the natural levels of the whole
The milk packaging is opaque so it can't be exposed to (UV) light.
The poor in the southern US consumed diets high in corn. Niacin is bound to a protein in corn
and is not bioavailable. Lime hydrolyzes the bond between the niacin and the protein.
Not everyone can tolerate 50 mg of niacin, so they experience these side effects.
Vitamin B6 is related to amino acid metabolism. There are coenzymes that require vitamin B6
for the transamination (e.g., transfer of amino group from one amino acid to another). You start
with an essential amino acid and you convert it to a non-essential amino acid. You can
completely remove the amino group completely, which is the reaction that occurs when you are
breaking down muscle to produce glucose. This will often happen in the fasting state, where you
run out of glycogen stores and the only way your body can maintain blood glucose levels is to
start breaking down the body proteins.
Sometimes vitamin B12 functions in the decarboxylation reaction, which converts amino acids
Folate was identified as being a vitamin that we have difficulty getting into our diet. The main
source of folate is fruits and vegetables. For the prevention of neural tube defects, it was found
that the levels of folate required might be beyond what most of the population can obtain from
their food supply. Folate is added to white flour, pasta, and cereal products to ensure that we
have an adequate supply of folate to prevent neural tube defects. Vitamin B6, B12, and folate tend to function together. The three of them are found in common
metabolic pathways. Sometimes you can restore a deficiency in one, but still have problems with
the metabolic pathway because of deficiencies in the remaining two vitamins.
This illustrates the importance of synergy. Vitamins act together in a combined form to affect a
metabolic change. You have to be mindful of the intake of all three of those nutrients to ensure
that these metabolic functions are behaving properly.
Homocysteine is an amino acid that is produced as a result of post-translational modification.
Homocysteine is a sulfur containing amino acid, and is derived from the metabolism of
methionine. The hypothesis is that because vitamin B6, B12, and folate help to keep the level of
homocysteine low, then if you increase the intake of these vitamins, then you will reduce the risk
of CVD. Vitamin B6 is probably the one out of the three vitamins that we don't need to worry
that much about. Vitamin B12 and folate are also integrated into this hypothesis. The concern is
with the intake of folate because it is the hardest to obtain of the three vitamins.
This is two these three vitamins interact. Homocysteine is a metabolic by-product of methionine.
Homocysteine has several metabolic fates. The homocysteine hypothesis is that if you keep
levels of homocysteine low, then you will reduce the risk of CVD. One way that this can be done
is through vitamin B6 mediated reaction, which converts homocysteine to cysteine, which goes
on to other metabolic pathways. Another way to eliminate homocysteine is to convert it to
methionine. To do this, you need a derivative of vitamin B12 called methyl-B12 (single carbon
group). You need a methylated form of vitamin B12. Methyl-B12 reacts with homocysteine,
which produces vitamin B12 and methionine. To get methyl-B12, you need to incorporate a
reaction that requires folate. The methyl group comes from a derivative of folate called methyl
folate. Methyl folate reacts with vitamin B12 to produce methyl-B12 and folate. Vitamin B6
converts folate into methyl-folate.
The reactions that require vitamin B12 do not function well unless you have folate. The reactions
that require folate also do not function well unless you have vitamin B12 (discussed later).
Vitamin B6 is also a player in this scheme. If you have adequate amounts of vitamin B12 and
folate, then you can keep your levels of homocysteine lower.
This is the missing piece of the puzzle. There are lots of reasons. In an observational study, you
are looking at younger populations. In an intervention trial, you recruit individuals who are
already at risk for CVD. There is the problem of dose. Observational studies use folate as a supplement. Intervention trials are often done at very high dosages of vitamins (e.g., doses that
are higher that you can get from your dietary intake, or even higher from supplements). This
means that you are using the vitamin as a drug, which will have different effects at higher levels.
This may interfere with or activate other metabolic pathways.
Folic acid (used to refer to the supplement) is a slightly different chemical than folate in food.
Folate is also important for the synthesis of RBCs.
Folate participates in DNA synthesis, which helps to drive RBC formation. In RBC formation,
we start with a RBC precursor (in bone marrow). if folate is adequate, then the RBC precursor
divides normally. The nucleus disappears to produce RBCs. RBCs are atypical in that they are a
cell that contains no nucleus and their proper formation involves the disintegration of the
nucleus, which is driven by appropriate DNA synthesis and appropriate gene expression.
If you are folate deficient, you end up with a cell that is unable to divide. Sometimes, you will
see fragments of the nucleus in the cell. You end up with a larger sized cell (macrocyte). This
type of anemia from folate deficiency is different from the anemia that you develop from iron
deficiency. Iron deficiency has to do with the synthesis of hemoglobin. This has to do with the
development of the RBC.
The brain and the spinal cord forms from inside the neural tube. Defects in the formation of the
neural tube will have extreme consequences in neurological development of the infant.
A low intake of folate and some genetic predisposition to poor metabolism of folate will result in
neural tube defects.
Fortification of folate in white flour, cornmeal, and pasta are mandatory. Fortification of folate in
breakfast cereals are not mandatory. Slide 26
DNA methylation (e.g., epigenetic effect) is believed to be the driving mechanism behind
controlling neural tube defects. DNA methylation allows for the appropriate and healthy closure
of the neural tube.
This shows the failure to close at the waist. If the failure to close is at the brain, then these are
neural tube defects that are fatal (e.g., without a brain, missing parts of the brain, parts of the
brain protruding out of the side of the head).
Mild cases can be corrected with surgery. Severe cases can be partly or fully paralyzed from the
waist down. It is a defect that has tremendous impact on someone's quality of life.
You can't completely get it down to 0%, perhaps because the best fortification program won't
capture every vulnerable person, but also because some neural tube defects are not driven by
nutrition deficicency, but driven by genetic mutation instead.
Folate levels in RBCs are the best way to measure folate status.
1) The percentage of the population that has folate levels at the folate deficiency cut-off is 0%.
Folate fortification has effectively eliminated megaloblastic anemia in Canada.
2) The percentage of the population that has a level of folate that is considered optimal to prevent
neural tube defects is 22%, which is our target with fortification programs. This means that 22%
of women of reproductive age still have a folate level that is lower than the cut-off. Almost 78%
of women have enough folate. This is a sign of a successful fortification program.
3) The high concentration cut-off is arbitrary. 60% of women fall below the high concentration
cut-off, but 40% are above the high concentration cut-off. We have a lot of Canadian men and
women with very high levels of folate.
Who are the people who are affected the most? Colon cancer mainly affects people who are over
50 years old. This is a different population than the women of reproductive age that the folate
fortification program targeted. We added folate to the food supply that everyone eats, regardless of age. This illustrates that you have to always keep in mind the too little and too much sides of
any kind of nutrient dose.
Colon cancer rates are declining from 1985-1998 perhaps because people are smoking less.
Smoking introduces carcinogens that can end up in the colon and induce cancer, not just the
lungs. In 1998, around the time when the folate fortification program stared, there is an increase
in colon cancer rates. It is hypothesized that there are individuals who are harboring the
beginnings of a colon tumor, and when we fortify our food supply with folate, it produces the
growth of a tumor. So we get diagnosis of the disease earlier than you might expected, or maybe
the stimulation of the growth of a tumor that might not have happened in that person's lifetime
otherwise. The increase of folate in the food supply may have stimulated tumor growth for the
few unfortunate people who are harboring a pre-existing cancer.
Folate is required for DNA synthesis, and cancer cells are rapidly reproducing cells that require
folate to make enough DNA to be able to continually proliferate.
Although fortification programs are largely beneficial, when adding nutrients to the food supply,
one has to be mindful of the U-shaped curve. Sometimes too much can be added to a food supply
and that can do some harm to potential subpopulations. In the case of folate, the concern might
be for adults over 50 who are more vulnerable to developing colon cancer.
A direct folate deficiency is that you are not getting enough folate in your diet. A secondary
folate deficiency is created indirectly because you don’t have enough vitamin B12. If you don’t
have enough vitamin B12, then you can’t convert methyl folate into folate, which then goes on to
produce normal blood cells.
Vitamin B12 tends to be concentrated in animal tissue. You need animal source foods in order to
get enough vitamin B12 in your diet. If you are a strict vegan, then you have to supplement with
vitamin B12. A small percentage of women of reproductive age who are vegetarian are
developing vitamin B12 deficiencies, which may compromise pregnancy.
Vitamin B12 produces pernicious anemia, which is symptomatically the same as megaloblastic
anemia. It is called pernicious anemia because its origin is due to vitamin B12 problems, rather
than due to the deficiency of folate. It is caused by the inability to absorb vitamin B12 properly.
Sometimes it is caused by an autoimmune disease that destroys the intrinsic factor (IF), which is
a protein that is needed for the absorption of vitamin B12. Pernicious anemia does not respond to iron supplementation because its origin is different from the anemia that people dev