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itamins are essential organic nutrients required in very small

amounts for normal metabolism, growth and physical well-


being. Most vitamins are not made in the body, or only in
insufficient amounts, and are mainly obtained through food.
When their intake is inadequate, vitamin deficiency disorders
are the consequence. Vitamins are present in food in minute
quantities compared to the macronutrients protein,
carbohydrates and fat. The average adult in industrialised
countries eats about 600g of food per day on a dry-weight basis,
of which less than 1 gram consists of vitamins.

No single food contains all of the vitamins and, therefore, a


balanced and varied diet is necessary for an adequate intake.
Each of the 13 vitamins known today has specific functions in
the body, which makes every one of them unique and
irreplaceable. Vitamins are essential for life!

Of the 13 vitamins, 4 are fat-soluble, namely vitamins A, D, E


and K. The other vitamins are water-soluble: vitamin C and the
B-complex, consisting of vitamins B1, B2, B6, B12, folic acid,
biotin, pantothenic acid and niacin.

The history of vitamins can be divided into five periods.


1. The empirical healing of diseases, now associated with
vitamin deficiency, through consumption of particular
foods. An example is the use of liver to treat night
blindness (vitamin A deficiency) by the Egyptians (Papyrus
Ebers 1550-1570 BC), Assyrians, Chinese, Japanese,
Greeks, Romans, Persians and Arabs.
2. The second phase was characterised by the ability to
induce a deficiency disease in animals, which started with
the classical studies of Lunin and Eijkman around 1890.
The ability to produce deficiency diseases, such as beriberi
in animals, led to Hopkins’ concept that small amounts of
“accessory growth factors” are necessary for growth and
life, and the coining of the term “vitamine” in 1912 by the
Polish-American scientist, Funk.

3. The third phase consisted in seven decades of exciting


research involving the discovery, isolation, structure
elucidation and synthesis of all the vitamins, and
culminating in the synthesis of vitamin B12 in 1972. Most
scientists think that the discovery of any new vitamin is
quite unlikely, although efforts are still continuing in that
quest. Many of the researchers involved in this golden age
of the vitamins received a Nobel prize in recognition of
their great achievements (Table 2)

4. During the era of discovery, a fourth period began which


was concerned with the biochemical functions,
establishment of dietary requirements and commercial
production. In the early 1930s it was realised that
riboflavin (vitamin B2) was part of the “yellow enzyme”,
which in time led to the elucidation of the role of the B-
vitamins as coenzymes. The subsequent identification of
most of the B-vitamins as coenzymes remained a central
theme, defining their function for many decades. The first
commercial synthesis of vitamin C by Reichstein in 1933
was the start of a successful industrial effort that led to the
availability of relatively inexpensive vitamins for research
and use in animal feedstuffs, for the fortification of food
products, and for supplements.

5. The accumulation of reports of health benefits beyond


preventing deficiencies and exciting new biochemical
functions of vitamins ushered in a fifth period, starting
with the report in 1955 of the cholesterol-lowering effect of
niacin (1). This is now a well accepted effect of the
vitamin, which has nothing at all to do with its classical
coenzyme role, and is a clear health effect beyond
preventing the deficiency disease pellagra.
Finally, work on the biochemical function of vitamins in the last
three decades has considerably expanded our concept of how
vitamins function in the body and has helped provide a chemical
basis for the in vivo observation of their health effects (Table 3).

Table 1: The History of Vitamins

Table 2: Vitamin-Related Nobel Prize Winners


Table 3: Biochemical Function of Vitamins

Vitamin B complex
By Venom

You would not be able to even type ABC into your browser without
ATP. In fact, within a few seconds death would wrought its ugly
head had this source of energy ceased to be produced. Think
logically for a moment; if this complex molecule is of such
importance, then its optimization must be of prime significance if
one is to train at full capacity--enter the B-Complex. It is integral to
almost every step of cellular respiration (energy production). Can
you afford a deficiency in this area? The answer is a clear no. I
must warn you, however, the body’s ability to form energy is
indeed complex beyond the readers wildest imaginations. It will
therefore be no easy task to understand all the mechanisms
capable of enhancing it. Today, however, you will take one giant
Leap forward--that is a guarantee.

Vitamins
Vitamins can be defined as essential organic compounds required
in minuscule amounts (referred to as micronutrients). Vitamins
mainly function as catalysts for reactions within the body. They
contain no useful energy, but as catalysts, they serve as essential
links and regulators in metabolic reactions that release energy
from food. Vitamins also control the processes of tissue synthesis
and aid in protecting the integrity of the cells' plasma membrane;
they also assist growth, maintenance of health, metabolism and
much more. To refresh your memory, a catalyst is a substance
that allows a chemical reaction to occur using less energy and
less time than it would take under normal conditions. If these
catalysts are missing, as in a vitamin deficiency, normal bodily
functions can break down hindering athletic performance, and
rendering a person susceptible to disease [7].

In the early part of the twentieth century, vitamins--then known as


"accessory growth factors,"--were discovered. The word 'vitamin'
is derived from the combination of words ‘vital amine’ and was
conceived by Polish chemist Casimir Funk in 1912. Funk isolated
vitamin B1 (thiamine) from rice [63].

However, vitamins achieved importance centuries before


scientists isolated and classified them. The Greek physician
Hippocrates (discussed in President Wilson’s suburb article,
Hippocrates - Was He Hardcore? ) advocated ingesting liver to
cure night blindness. While he did not know the reason for the
cure, we now know that vitamin A, which helps to prevent night
blindness, occurs plentifully in this meat. In 1897, a Dutch
physician in Java observed that a regular diet of polished rice
caused beriberi in fowl, while adding rice polishings (thiamine-
rich) to table scraps cured the disease. A most famous discovery
was found in the early 19th century, when it was observed that
adding oranges and lemons to the diet of British sailors paved the
way for eradicating the dreaded disease scurvy, because of the
protective effects of the vitamin C contained in the fruits. Not until
1932, however, did ascorbic acid (vitamin C) become isolated
from lemon juice [63].

The formal discovery of vitamins revealed that these organic


substances were needed by the body in minute amounts.
Vitamins, their amine role having been discredited, have no
particular chemical structure in common, and are often
considered accessory nutrients because they neither supply
energy, nor contribute substantially to body mass. Finally, with the
exception of vitamin D, which is formed with the help of ultraviolet
radiation, or sunshine, and some K and B vitamins, which are
produced by bacteria within our intestines, the body cannot
manufacture vitamins; hence, diet and or supplementation must
supply them [37,28].

Vitamin classification
Vitamins are classified as either fat-soluble or water-soluble. The
fat-soluble vitamins (vitamins that can mix with fat, but usually not
with water) are vitamins A, D, E, and K; the water-soluble vitamins
(can be dissolved/mixed in water) are vitamin C and the B-
complex vitamins (based on their common source distribution
and common functional relationships)[38]. Today we will narrow in
on the later group.

Water-soluble vitamins, with the exception of vitamin C, are


members of the B complex. Most of the B-complex group can be
further divided according to general function: energy releasing,
hematopoietic (refers to an agent or process that affects or
promotes the formation of blood cells) and others. Other vitamins
cannot be classified this narrowly because of their wide range of
functions [14].

The water-soluble vitamins act largely as coenzymes, with small


molecules combing with a larger protein compound (apoenzyme)
to form an active enzyme that accelerates the interconversion of
chemical compounds. Coenzymes participate directly in chemical
reactions; when the reaction runs its course, coenzymes remain
intact and participate in additional reactions. Water-soluble
vitamins, similar to their fat-soluble counterparts, consist of
carbon, hydrogen, and oxygen atoms. They also contain nitrogen
and metal ions including iron, molybdenum, copper, sulfur, and
cobalt. Because of their solubility in water, water-soluble vitamins
disperse in the body fluids without being stored to any appreciable
extent. If the diet regularly contains less than 50% of the
recommended values for water-soluble vitamins, marginal
deficiencies may develop within 4 weeks [89,88,90,12,13].

Water-soluble vitamins are absorbed into portal blood;


furthermore, with the exception of cyanocobalamin (vitamin B12),
they cannot be retained for long periods by the body. Any storage
occurring results from their binding to enzymes and transport
proteins. Generally, an excess intake of water-soluble vitamins
becomes voided in the urine. Water-soluble vitamins exert their
influence for 8 to 14 hours after ingestion; thereafter, their potency
begins to decrease. For maximum benefit of, for example, vitamin
C supplements, they should be consumed at least every 12
hours. Sweating during extreme physical activity can produce
negligible losses of the water-soluble vitamins as well [3,5].

Finally, let us venture into today’s subject, the water-soluble


substances known collectively as, ‘Vitamin B complex.’

Vitamin B complex
B-complex consists of eight different vitamins, which
include thiamine (B1), riboflavin (B2), niacin (B3),
pantothenic acid (B5), piroxidine (B6), folic acid (B9),
cyanocobalamin (B12), and biotin. All of the above are
water soluble, and play a key role in several bodily
functions, such as protein, fat, carbohydrate, and
mitochondrial energy metabolism; maintenance of the
liver, skin, hair, mouth, and eyes; plus so much more,
which will be covered thoroughly within the following
paragraphs. As mentioned above, vitamin b complex can
be further broken down in to 3 general categories; that is,
energy releasing, hematopoietic, or other. And some fit in
both categories. Here is a list [7,12]:
Energy releasing- Thiamine (B1), Riboflavin (B2), Niacin
(B3), Pantothenic acid (B5), Piroxidine (B6), and Biotin.
Hematopoietic- Folic acid (B9), Cyanocobalamin (B12),
Pantothenic acid (B5), and Piroxidine (B6).
Other- Thiamine (B1), Niacin (B3), Piroxidine (B6), Folic
acid (B9), and Cyanocobalamin (B12).
All of these factors will be understood, after this article.
Before we begin, here is an outline of what will be covered
on each of these 8 powerhouses.
· Description- the chemical makeup and structure of
each vitamin
· Digestion- how these micronutrients are digested in
the human body.
· Function- A complete dissection of the process by
which they benefit the body
· Deficiency- the problems caused by a deficit in any
of the B-complexes
· Recommendation- within I will list food sources that
contain them, recommended doses, toxicity levels,
and much more.
For full comprehension of this article, I would highly
recommend you read last month’s issue of hyperplasia, as
many of the terms and physiological occurrences are
discussed therein.
Thiamine (B1)
The first aspect of the B-complex we will cover is Vitamin B1. The
first to publish a correct formula and synthesis for this vitamin was
Dr. Robert R. Williams in 1936. Synonyms for it are thiamine,
thiamin and aneurin. Chemically, Thiamine consists of a
pyrimidine ring and a thiazole moiety (or one of two parts) linked
by a methylene (CH2) bridge. As stated above, it is water-soluble
[63,44].

Digestion
Thiamin can travel by both active (through plasma membrane,
requires metabolic energy to “power” the exchange of materials)
and passive (through plasma membrane, requires no energy)
transport, depending on the amount of the vitamin presented in
the intestine for absorption. At low physiological concentrations,
thiamin absorption is active and sodium-dependent (type of active
transport). Absorption occurs primarily in the upper jejunum but
can occur in the duodenum and ileum (portions of the small
intestine). When intakes of thiamin are high, absorption is
predominantly passive [101, 88, 83].

Transport of thiamin into red blood cells is thought to occur by


facilitated diffusion (diffusion that is assisted by protein
transporters). Only free thiamin or thiamin-monophosphate (TMP)
is thought to be able to cross cell membranes. In red blood cells,
most thiamin exists as thiamin-diphosphate (TDP) with smaller
amounts of free thiamin and TMP.

The human body contains approximately 30 mg of thiamin, with


relatively high but still small concentrators found in the skeletal
muscles, heart, liver, kidney, and brain. In fact, skeletal muscles
are thought to contain about half of the body's thiamin [107].

Following absorption, most free thiamin is taken up by the liver


and converted to its coenzyme form, thiamin-diphosphate (TDP).
Conversion of thiamin to TDP requires adenosine triphosphate
(ATP) and thiamin pyropbospbokinase, an enzyme found in the
liver, brain, as well as other tissues. About 80% of total thiamin in
the body exists as TDP, 10% as TTP (thiamin triphospate), and
the rest is TMP, which is inactive [88, 83, 2].

To understand transport systems, as well as more information on


the digestion track, it would behoove the reader to study the
following articles: Sodium - A comprehensive Analysis &
Fiber Dynamics Part I.

Next, we will show how Vitamin b1 functions in the body, and its
many beneficial traits.

Function
Vitamin b1 is absolutely essential to several bodily functions. We
will break them down into 2 categories consisting of:

• Energy metabolism
• Nervous system

Energy metabolism
The Krebs cycle (also called the citric acid cycle and the
tricarboxylic acid cycle) is extremely important in
extracting energy from fuel molecules. Consequently, the
process is thiamin dependent. TDP functions as a
coenzyme (binds with certain protein molecules to form
active enzymes) necessary for the oxidative
decarboxylation of both pyruvate and a-ketoglutarate.
These reactions are instrumental in generating energy
(ATP). Inhibition of these decarboxylation reactions
prevents synthesis of ATP, and of acetyl CoA needed for
the synthesis of, for example, fatty acids, cholesterol, and
other important compounds, and results in the
accumulation of pyruvate, lactate, and a-ketoglutarate in
the blood [35,26,25].
Failure to oxidize the molecules listed above (and several
others), results in the accumulation of both the branched-
chain amino acids and their a-keto acids in blood and
other body fluids. This is characteristic of maple syrup
urine disease (MSUD). MSUD results from a genetic (in-
born error of metabolism) absence or insufficient activity of
the branched-chain a-keto acid dehydrogenase enzyme
complex. People with MSUD must avoid meat, poultry,
fish, and dairy products to limit intakes. But in short,
thiamin is vital for energy conversions, and if lacking in
your diet and supplementation, can induce serious health
problems, and inefficiencies in the iron jungle.
Concerning this topic, Sanz Paris A et. al states, “In
thiamine deficiency, the Krebs cycle slows large quantities
of pyruvate are diverted to lactate production and
anaerobic metabolism begins [99].” Timm DE et. al states,
“Thiamine is essential for central metabolic processes,
including the formation of acetyl CoA from glucose and the
Krebs cycle. Deficiencies in human thiamin metabolism
result in beriberi and Wernicke encephalopathy[26].”
Thiamin assists many other bodily functions, such as
synthesis of pentose, NADPH, and additional molecules.
All of which are essential for fatty acid synthesis, cell
replication and much more. Here is an additional quote
form La Selva M et. al [100], “Thiamine restores cell
replication, decreases the glycolytic flux and prevents
fluorescent AGE formation in endothelial cells cultured in
high glucose”

Nervous system
It is apparent from several neurological disorder studies
concerning thiamine deficiency, and taking into account
where thiamine is found (in both the nerves and brain),
that this vitamin plays a vital role in nerve function. Ke ZJ
et al. states [19], “results indicate that TD [thiamine
deficiency] induces alterations in neurons, endothelial
cells, and microglia contemporaneously. This model
provides a unique paradigm for elucidating the molecular
mechanisms involved in neuronal commitment to neuronal
death cascades and contributory microglial activity.”
What the exact role is has yet to be determined. But there
are many viable theories currently being investigated. One
theory is that thiamine triphosphate helps regulate nerve
impulses, via the Na+ and K+ gradient. And other
important channels, helping to regulate functions through
many reactions. Also, it is thought to act as a coenzyme in
the production of neurotransmitters (chemical messengers
between nerve fibers). Either way, results have
consistently revealed that being deficient in this vitamin is
highly detrimental to the function of your nervous system,
making this a vital supplement [55,46,17,16,].

Deficiency
Deficiency of aneurin can cause serious ailments. One of the first
symptoms of thiamin deficiency is a loss of appetite (anorexia)
and thus weight. As deficiency worsens, cardiovascular system
involvement (such as hypertrophy and altered heart rate) and
neurological symptoms appear.

One major symptom of B1 deficiency is an ailment called,


‘beriberi’. There are three types of beriberi classified today:

• Dry beriberi- found predominantly in older adults; it is


thought to result from a chronic low thiamin intake especially
if coupled with a high carbohydrate intake. Dry beriberi is
characterized by muscle weakness and wasting, especially
in the lower extremities
• Wet beriberi- results in more extensive cardiovascular
system involvement than dry beriberi; right-side heart failure
leads to respiratory involvement with edema.
• Acute beriberi- seen mostly in infants has been documented
in countries such as Japan.

In the United States and in Western countries, thiamin deficiency


associated with alcoholism is common and is referred to as
'Wernicke's encephalopathy' or 'Wernicke-Korsakoffa syndrome'.
Individuals with dependency on alcohol are particularly prone to
thiamin deficiency because of:

• Decreased intake of the vitamin due to decreased food


consumption.
• An increased requirement in the case of liver damage
(decreased liver function impairs mp formation and,
consequently, vitamin use); and
• Decreased thiamin absorption

Wernicke's encephalopathy, often manifested in those with a


history of alcohol abuse, is characterized by ophthalmoplegia
(paralysis of eye muscles), nystagmus (involuntary, rapid,
rhythmic movement of eyeball), ataxia (Failure of muscular
coordination, irregularity of muscular action), loss of recent
memory, and confusion. Treatment consists of therapeutic doses
(at least 100 mg) of thiamin [112,101,100].

Recommendations
Because of thiamin’s importance in energy metabolism, needed
intake varies according to energy (caloric) intake. The RDA for
adults is 0.5 mg/ 1000 kcal; however, an intake of no less than 1
mg/day is advised. The 1998 Dietary Reference Intakes RDA for
individual intake for thiamin for adult men aged 19 years and older
is 1.2 mg/day and for adult women aged 19 years and older 1.1
mg daily. Thiamin in-takes with pregnancy and lactation (secreting
milk) are increased to 1.4 and 1.5 mg/day, respectively [113,47].

As far as over consumption is concerned, there appears to be


little danger of thiamin toxicity associated with oral intake of large
amounts (500 mg daily for 1 month) of thiamin.

Pharmacological levels of thiamin are used in the treatment of


certain inborn errors of metabolism. One variant form of MSUD
has been shown to respond to oral thiamin supplements (up to
500 mg daily). Other metabolic diseases that may respond to
large doses of the vitamin are thiamin-responsive megaloblastic
anemia id and thiamin-responsive lactic acidosis. In the latter
condition, large doses of thiamin can increase the activity of
pyruvate dehydrogenase in the liver, thereby decreasing the level
of lactic acid, as more pyruvate is decarboxylated for entry into
the Krebs cycle [4].

Finally, thiamin is widely distributed in foods, including meat


(especially pork), legumes, and whole or enriched grain products.
Yeast and wheat germ also contain significant amounts of this
vitamin [110,98].
Riboflavin (B2)
B2, known as Riboflavin, is constructed of flavine (a ring, acts as
a covalent link), which is attached to a sugar alcohol, formed by
the reduction of ribose called ribitol. And once again, it is a water-
soluble vitamin.

Digestion
Riboflavin is primarily absorbed in the proximal small intestine by
a sodium dependent carrier. Within cells, b2 is converted to its
coenzyme forms, regulated by hormones, such as the thyroid
hormone. These coenzymes, than bind to apoenzymes (an
enzyme, which needs a co-enzyme to be activated) forming what
is called a flavoprotein (discussed below) [62,61,60,59].

Function
FMN and FAD (flavoproteins) are the principle forms of riboflavin.
They are coenzymes, and used in several actions, particularly in
the oxidation (reactant that accepts electrons from another
reactant) of agents, vital for many process to occur. Here is a list
of the many uses of vitamin b 2 [111,79,59,29]:

• Like thiamin, it acts as a coenzyme in the breakdown of fats,


proteins, carbs, and other nutrients.
• Helps fatty acid reduction. CoA needs FAD to accomplish
this.
• Assists choline catabolism.
• Required for neurotransmitter (such as dopamine, and
others) oxidation.
• Necessary for catabolism of nutrients in the liver.
• Helps b6 (discusses shortly) in many reactions, as it is often
FMN dependent.
• Assists eye and skin maintenance.

Deficiency
There is no exact understood mechanism for disease related to
b2 deficiency; however, clinical symptoms of deficiency after
almost four months of inadequate intake have shown
inflammation of the tongue, loss of function on the outside of the
lips and at the sides of the mouth, sore throat, a red or
bloody/puffy mouth, inflammation of skin, eyes become light
sensitive, and nerve dysfunction, to name a few.

Extreme lack of riboflavin may slow the synthesis of the


coenzyme form of vitamin B6 and niacin synthesis (later
discussed within this article). Conditions and populations
associated with increased need for riboflavin intake are many.
Deficiency often occurs with heart disease, some cancers, thyroid
disease, and excess alcohol intake. Women on pregnancy pills
are also more likely to develop deficiency than women not taking
these drugs. Concerning this topic, Wacker J et. al states [80]:

“Riboflavin deficiency should be considered a possible


risk factor for preeclampsia. Insufficient concentrations
of the riboflavin-derived cofactors flavin adenine
dinucleotide and flavin adenine mononucleotide could
contribute to the established pathophysiologic changes
including mitochondrial dysfunction, enhanced
oxidative stress, and disturbances in nitric oxide
release.”

Finally, have you ever noticed when taking a multi vitamin, or


perhaps a vitamin b supplementation pill, your urine-changed
color? This is due to riboflavin. Riboflavin is a fluorescent yellow
compound. Ingestion of this will most likely induce a change in
urine color, to light yellow/bright orange. Also, small amounts of
vitamin b2 are secreted in the feces, causing a yellowish color.
This side effect is harmless though, so you can put your mind at
ease when this occurs [113,59,32].

Recommendation

The 1989 RDA for riboflavin is given in milligrams per 1,000 kcal.
The recommended allowance for people of all ages is 0.6 mg/
l,000 kcal with a minimum intake of 1.2 mg for persons whose
caloric intake may be more than 2,000 kcal. Through the years,
the recommended allowances for riboflavin have been calculated
in relation to:
• Protein requirement,
• Energy intake
• Metabolic body size.

Because of the interdependence of these three variables,


allowances calculated by the various methods have not differed
significantly. The 1998 DRI RDA for individual intake for riboflavin
is similar to the 1989 RDA. The DRI RDA for adult men and
women aged 19 years and older for individual intake for riboflavin
is 1.3 and 1.1 mg/day, respectively. With pregnancy and lactation
the DRI for daily riboflavin intake increases to 1.4 and 1.6 mg,
respectively. Toxicity associated with large oral doses of riboflavin
has not been reported. Good sources of Vitamin B2 are eggs,
meat, legumes, milk, and milk products such as cheese [80,67].

Niacin (B3)
Niacin, also known as nicotinic acid nicotinamide, and vitamin b 3,
is a water-soluble vitamin, and apart of the b-complex.

Digestion

In the human body, niacin is broken down to Nicotinamide


adenine dinucleotide phosphate (NADP), and nicotinamide
adenine dinucleotide (NAD). These are the primary forms which
niacin functions within the body.

In the intestine, NAD and NADP may be hydrolyzed to release


free nicotinamide. This can be absorbed in the stomach, but
primarily in the small intestine. In low concentrations, free
nicotinamide is absorbed by a sodium dependent carrier. In high
concentrations, it uses passive diffusion.

Most of the niacin in the blood is found as nicotinamide, a small


amount of the time as nicotinic acid. From here, they move
through the cell via a sodium dependent carrier system
[107,85,57,56,15]

Function

Almost 200 enzymes require NAD and NADP to function. To


name a few B3 functions, NAD helps glycolysis, oxidation of
pyruvate, acetyl CoA by the kreb cycle, and fatty acids. NADP
assists with fatty acid synthesis, cholesterols and steroid
synthesis, oxidation of glutamate, and DNA synthesis. Some
enzymes which require NADP are glutathione reductase,
dihydrofolate, and tetrahydrofolate [107,56,43,33].

For much more on NAD in relation to energy metabolism, read,


Energetic Transference Occurring in the Biosphere Part II:
Anaerobic Energy Pathways.

Deficiency

Deficiency of niacin often results in a condition known as pellagra.


The side effects are known as four d’s; dermatitis (inflammation of
skin), dementia (a mental disorder characterized by a general loss
of intellectual abilities involving impairment of memory, judgment
and abstract thinking as well as changes in personality), diarrhea,
and death. Dermatitis is much like a sunburn at first and appears
on areas exposed to sun such as the face and neck and on the
extremities such as the back of the hands, wrists, elbows, knees,
and feet. Some neurological problems are paralysis of
extremities, and dementia (the second D) or delirium. Several
gastrointestinal problems may occur such as nausea, vomiting,
and diarrhea (the third D). Ultimately, if this problem is not treated,
death occurs. A poor diet, and excess alcohol leads to increased
niacin needs; as does stress, trauma, and prolonged fevers
[64,30,3]. Concerning this topic, Spronck JC and Kirkland JB, said
this [27]:

“These data show that niacin is required for the


maintenance of chromosomal stability and may
facilitate DNA repair in vivo, in a tissue that is sensitive
to niacin depletion and impaired pADPr metabolism.
Pharmacological intakes of niacin do not appear to be
further protective compared to adequate intakes. Niacin
supplementation may help to protect the bone marrow
cells of cancer patients with compromised nutritional
status from the side effects of genotoxic chemotherapy
drugs.”

Recommendation

The 1989 RDA for adults is 6.6 mg of niacin per 1,000 cals
consumed. The DRI RDA recommends at least 16 mg per day.
For pregnancy and lactation, the DRI RDA recommends 18 mg a
day. Up to 35 mg a day has been suggested. For high cholesterol,
up to 3 g of nicotinic acid per day has been applied. The
mechanism of action for lowered cholesterol is not clearly
understood; it is proposed that nicotinic acid decreases the levels
of camp in the adipocytes, thereby decreasing lipase activity.
Decreased lipase activity results in a decreased mobilization of
fatty acids from the adipocytes and, therefore, a decreased
substrate for synthesis of very low-density lipoproteins (VLDLs) in
the liver. Decreased production of VLDLs lowers
triacylglycerollevels, because VLDLs contain relatively high
amounts of triacylglycerols. Furthermore, with decreased VLDLs
there is less synthesis of LDL (bad cholesterol) and thus lower
serum cholesterol levels. An increase in the HDL (good
cholesterol) appears to be due to a decrease in their breakdown
within the liver [113,107,70].

Concerning mega doses, consuming 1g and above may induce


[67,54]:

• Release of histamine, which causes flushing and is bad for


people with asthma. Sometimes this may occur with as little
as 10 mg.
• Raises acidic levels in body.
• Induces itching.
• Raises glucose levels
• May injure liver by obstructing flow of nutrients to the small
intestine.

Up to 500 mg of niacin appears to give relatively no


adverse effects. Niacin may be found in dairy products,
poultry, fish, lean meats, nuts, and eggs. Legumes and
enriched breads and cereals as well [64].
Pantothenic acid (B5)
Pantothenic acid is derived from the Greek word
"pántothen", meaning "from all quarters," and as its name
depicts, it is found present in virtually all plants and animal
foods, hence, deficiency is not likely. It is part of the
chemical makeup of Coenzyme A. It is also known in other
forms -Calcium Pantothenate, Pantothenate, and
Panthenol [74,63].

Digestion

This vitamin occurs mainly as coenzyme A. It is primarily


absorbed in the small intestine via passive diffusion.
Transportation in the heart, muscles, and liver cells is
done by a sodium active transport. Within the central
nervous system, adipose, and renal uptake, facilitative
diffusion is used [74,42,12].

Function

Synthesis of CoA is dependant on Pantothenic acid. As


discussed throughout this article, CoA is used in many
reactions, such as the kreb cycle, and production of
energy from carbohydrates, proteins, and lipids. It also
assists metabolism of certain drugs, skin, and steroids.
Studies have show than Vitamin b5 may accelerate the
normal healing process after surgery [78,76,75]. Here is
one study by Taherzadeh MJ [73] “Physiological effects of
deficiency of pantothenate, a necessary precursor in the
synthesis of coenzyme A, were studied… the time
required for complete conversion of the glucose
decreased by 40%. Acetate addition affected the acetate
and glycerol yields in a similar way in pantothenate-rich
medium”

Deficiency

Deficiency usually occurs with people who are severally


malnutritioned, along with alcoholics, diabetics, and
certain bowel diseases. Side effects are vomiting, fatigue,
weakness, and a burning feet syndrome, characterized by
abnormal skin sensations [33,7,6,69].

Recommendation

The DRI recommends 5 mg a day for adults. For certain


conditions such as pregnancy, 7 mg’s a day is
recommended. Concerning side effects, intakes of 100 mg
a day for Vitamin b 5 may increase niacin excretion. 10 g a
day (besides niacin excretion) has exhibited no side
effects. 20 g a day may cause some intestinal distress,
and diarrhea. Pantothenic acid can be found in egg yokes,
legumes, whole grains, mushrooms, broccoli, avocados,
and several plants and meats [113,77,69,7,6].

Pyridoxine (B6)
The b-complex Pyridoxine, is a water-soluble vitamin. It was
discovered in 1934 by P. Gyorgy. Its composition is complex;
made of several vitamers (one of two or more similar compounds
capable of fulfilling a specific vitamin function in the body) its 3
major forms are pyridoxine (PN), pyridoxal (PL), and
pyridoxamine (PM). These vitamers are comparable in function,
and quite often interchangeable within a given reaction [63].

Digestion

For digestion to occur, vitamin b must be broken down, and


separated into its 3 main components pyridoxine, pyridoxal, and
pyridoxamine. This occurs in the intestinal brush border, via
enzymatic reactions. Absorption occurs primarily in the jejunum
(middle portion of small intestine, connects with the duodenum
(first portion) and the ileum (last portion) of the small intestine) by
passive diffusion. In the intestine, PN is converted to pyridoxine
phosphate (PNP), PL is converted to pyridoxal phosphate (PLP),
and PNP is often converted to PLP, while PM remains the same,
and composes about 15% of the vitamers in the blood. 60% of
vitamin b 6 found in the blood is PLP. In order for PLP to cross the
cell membrane it must be broken down to PL. The liver stores
approximately 10% of vitamin b 6, while muscles store the most at
80%. Other storage houses are the kidneys, brain, and red blood
cells [7].

Function

B6 acts as a coenzyme for approximately 100 essential chemical


reactions. These include protein and glycogen metabolism, proper
action of steroid hormones, pyruvate production, production of red
blood cells and much more. It assists in many decarboxylation
reactions (removal of carboxyl group) for the production of several
compounds such as glutamate (major neurotransmitter of the
central nervous system). It also is of great use to the immune
system in that it helps hemoglobin production and increases the
amount of O2 carried by it. Also, it assists white blood cell
production, all of which is vital for your health. Ortiz A et. al reports
that [1], “Vitamin B6 is essential for cellular functions and growth
due to its involvement in important metabolic reactions.”

Pyridoxine is additionally responsible for the synthesis of many


compounds. For example, niacin depends on a PLP dependant
reaction to be broken down. Others required by Pyridoxine for
synthesis are amino acid histidine, carnitine, nitrogen containing
compounds, CoA and glycine taurine, dopamine, and helps
regulate neurotransmitters, playing a major role in the nervous
system.

Finally, it appears PLP helps glycogen degradation. This theory is


in its infancy, but studies show that it acts as a protein buffer to
help maintain the compound, and promote covalent bonds to form
glucose [102,97,7].

Deficiency

Signs of deficiency are fatigue, glossitis (sore tongue) sleepiness,


dermatitis (skin inflammation), neurological problems, eye
problems, seizers, kidney and heart diseases, and convulsions in
infants. Tryptophan and niacin synthesis will be slowed as well.
People more likely to be deficient in this are infants, old people,
excessive alcohol consumption, those on a variety of drugs, and
certain medical conditions. High protein intake and stress may
inhibit this as well.

Also, a deficiency in B6 has been shown to increase the amino


acid homocysteine found in the blood. Studies have shown that
an excess of this protein can inflict blood clotting, and promote
heart disease/strokes [53,36,31].

Recommendation

B6 consumption is based on protein intake, the RDA recommends


.0016 mg of Vitamin b6 per 1 gram of protein. The DRI RDA
recommends at least 1.3 mg for young male adults, and 1.7 for
those 50 and over. For female adults and those over 50, they
recommend 1.3 and 1.5 g respectively [87,86]. 100 mg per day is
the upper intake for adults. Many doctors suggest 100-200 mg a
day of b6 to treat carpal tunnel disease (A condition where there
is a disturbance of median nerve function in the wrist as the nerve
passes through the carpal tunnel.). There have been innumerable
studies, which show its effectiveness. Ellis JM et. al states the
following from two scientific journals [105, 102],:

“It is concluded that patients with a severe syndrome


including the carpal tunnel defect have a deficiency of
vitamin B6, and that both the syndrome and the
deficiency are relived by therapy with pyridoxine.”
“ In my practice, vitamin B6 (pyridoxine) therapy (100 to
200 mg daily for 12 weeks) has proved curative for a
large percentage of patients having carpal tunnel
syndrome (CTS). Laboratory determination of the
vitamin B6 status has been useful in diagnosing
deficiency and in making decisions relative to surgery.
This paper directs particular attention to prevention of
CTS during pregnancy and discusses changes in
symptoms during the course of treatment of CTS with
vitamin B6.”

Scientist Laso Guzman FJ had this to say from his experiment


[23]:

“Twelve patients with carpal tunnel syndrome were


studied. Clinical and electrophysiological data were
obtained and an estimation of vitamin B6 (pyridoxine)
status by an assay of erythrocyte aspartate
aminotransferase and coenzyme stimulation assay
were done. None of the patients was found to have
vitamin B6 deficiency. Patients were treated with 150
mg of pyridoxine daily for 3 months. Erythrocyte
aspartate aminotransferase increased significantly (p
less than 0.001) in all the patients. In 6 patients there
were clinical and electrophysiological improvement and
erythrocyte aspartate aminotransferase increased more
than in the other 6 patients. The data obtained appear
to indicate that although vitamin B6 deficiency is not
common in carpal tunnel syndrome patients, pyridoxine
supplementation can be recommended as adjuvant
treatment in those patients undergoing surgery.”
Here is an excellent quote from Folkers K et. al, who makes a
very bold claim [103]:

“Blood samples from four patients at the time of surgery


to relieve the compression of the carpal tunnel
syndrome, which was diagnosed by clinical and
electromyographic evaluation, were differentially
assayed to determine the specific activities and the %
deficiencies of the erythrocyte glutamic oxaloacetic
transaminase (EGOT). The data from these assays
revealed that these four patients had a severe
deficiency of vitamin B6. These data, in conjunction
with previous biochemical and clinical results over five
years, underscore the desirability, and even necessity,
of testing by the EGOT analysis for the presence of a
severe deficiency of vitamin B6 in all such patients
before surgery. Treatment with vitamin B6 (pyridoxine)
for a minimum period of 12 weeks, depending upon the
duration and severity of the symptoms, has been
effective without exception.”

Kasdan ML et. al came to the same conclusion [24]:

“We reviewed 1075 patients presenting over a 12-year


period with symptoms of carpal tunnel syndrome. A
total of 994 had a final diagnosis of carpal tunnel
syndrome. There were 444 male and 550 female
patients with a mean age of 42 years. Three-hundred
and ninety-five related symptoms to their job. Surgery
was performed in 27 percent of the total diagnosed
cases with approximately 97 percent relief of
symptoms. Satisfactory alleviation of symptoms was
obtained in 14.3 percent of patients treated
conservatively prior to 1980, with one or a combination
of splinting anti-inflammatory agents, job or activity
change, and steroid injections. In 1980, vitamin B6
(pyridoxine) was added as a method of conservative
treatment. Satisfactory improvement was obtained in
68 percent of 494 patients treated with a controlled
dosage (100 mg b.i.d.). While our findings were not the
result of a controlled scientific study, we feel they
suggest that regulated use of vitamin B6 may be helpful
in treating many cases of carpal tunnel syndrome.”

In conclusion, though the exact mechanism has not yet been


determined, it is clear through hundreds of experiments that
pyridoxine plays a significant role in the treatment of carpal tunnel
syndrome. Another, similar problem known as Tarsal Tunnel
Syndrome (Compression of the posterior tibial nerve caused by
thickening of the laciniate leading to symptoms of pain or
paresthesia over the sole of the foot) is also often treated with B6.

Finally, due to its wide variety of functions in the nervous system,


such as production of neurotransmitters dopamine, serotonin,
supplementation of this vitamin is often suggested for treating
abnormal nerve sensations in the legs, arms, and other bodily
functions. Along with headaches, and states of depression
[103,81,66,67,24,23,22,21,20].
Concerning overdoses, 200 mg a day appears to have no
adverse effects. But 500 mg inflicts some neuro toxicity. And 1-6
grams daily has been shown to result in several side effects such
as ensory and peripheral neuropathy (dysfunctions in nervous
system) including numbness of the feet and hands, unsteady
movement, abnormal sensations of the dorsal root ganglia (group
of nerves) in the spinal cord, impaired tendon reflexes, and
degeneration of sensory fibers.

Pyridoxine is found in poultry, fish, pork, eggs, soybeans, oats,


whole-grain products, nuts, seeds and bananas [66,53,36,31].

Folic acid (B9)


Folic acid is named after the Latin word, “folium” for leaf. This
vitamin was discovered by DR. Lucy Wills, while researching how
to prevent anemia (loss of red blood cells) during pregnancy.
Synonyms for folic acid are vitamin B9, folacin, Pteroylglutamate,
Pteroylmonoglutamate, and folate. B9 is composed of 3 parts;
pteridine connected to paraaminobenzoic acid (PABA), which
forms Pteroic acid. Finally, Pteroic acid is connected to glutamic
acid to form folic acid. These compounds must be present for
activation of vitamin B9 [68,63].

Digestion
To be absorbed, B9 must be broken down to monoglutamate. This
occurs in the small intestine by the enzyme conjugase. This
process is zinc dependent--a deficiency in zinc will inhibit this
process. Absorption primarily occurs in the jejunum of the small
intestine, and is sodium dependent. In the blood, folate is
primarily found as monoglutamate. Throughout the body, B9 is
reduced to several forms such as THF, N5/N10 Methyl THF, among
others. The liver stores the majority of folic acid [108,91,52,18,9,].

Function

Health News stated [45], “Folate delivers head-to-toe health


advantages.” Lets see what exactly these are. Folate helps in the
metabolism of several amino acids such as histidine, glycine,
serine, and methionine. These processes will be discussed
subsequently [92,71,8,7].

Histidine
Histidine (an amino acid) can be broken down to uronic acid; this
can further be reduced to formiminoglutamate (FIGLU). This with
the help of THF can further be broken down to glutamic acid.
When deficient in Pteroylglutamate, FIGLU accumulates, instead
of being converted, and used as glutamate (as stated early, this is
vital for nervous function).

Glycine and Serine


Folate in the form of N5 and N10 (discussed above) is necessary
for both glycine, and serine synthesis (valuable amino acids used
in the metabolism of fats, carbs, muscular growth, immune
system, and much more) and degradation. It also helps activate
enzymes such as pyridoxal phosphate (PLP) to complete the
reactions.

Methionine
THF is required for breakdown of homocysteine to methionine.
Tying the article together, folate, vitamin B 12 (discussed next),
and B6, all show to play a role in this process. Research shows
that high homocysteine concentrations promotes heart disease.
An experiment revealed supplementing with these 3 vitamins
reduced homocysteine concentrations by 50%!

Other

Folic acid is essential for cell division, production of DNA and


RNA, and assists the prevention of changes in DNA, which may
lead to cancer.

Deficiency

Deficiency of folic results in anemia, depression, dementia,


increased rate of heart disease and cancer, loss of appetite,
weight loss, to name a few. People with increased folate needs
are the elderly, alcoholics, bowel diseases, pregnant and lactating
(secretion of milk) women, and the ingestion of certain drugs [68-
70]. Additionally, Rami;rez T et. al states [82], “Deficiencies of folic
acid and methionine, two of the major components of the methyl
metabolism, correlate with an increment of chromosome breaks
and micronuclei.”

Recommendation

The DRI RDA recommends 400 ug for adults. With an additional


200 and 100 ug for pregnancy lactation respectively.

Concerning side effects, studies suggest no side effects of


consuming 400 mg of folate per day. However, some studies are
contradictory to this, showing 15 mg of folate daily induce
insomnia, irritability, diminished zinc status, and gastrointestinal
distress. Toxicity for oral supplementation has not been reported.
5,000 ug of folate a day can mask B12 deficiency. Alleviating
anemia, but at the same time, masking neurological inflictions that
are due to B12 deficiency. It is recommended that if you are 50
years old, to ask a doctor to monitor your B12 level. But in short,
make sure you are consuming proper amounts of B12, and these
problems will not exist. Sources of folic acid include mushrooms,
green vegetables such as broccoli, spinach and asparagus, as
well as fruits grains, and legumes (particularly lima beans)
[68,34].

Cyanocobalamin (B12)
Vitamin B12, also called cobalamin, and cyanocobalamin, is an
active coenzyme, vital for many reactions, discussed shortly.

Digestion

First, B12 is acted upon by a salivary enzyme in the stomach. It


then proceeds to combine with a protein known as ‘R-protein’
called intrinsic factor before entering the small intestine. After this,
a pancreatic enzyme called trypsin separates it from the protein.
Then, it is combined with another protein, and from there the
ileum absorbs 70% of it, mainly by passive diffusion. After
absorption, B12 is binded to one of 3 R proteins called TCI, TCII,
or TCIII in the blood. About 90% of cyanocobalamin found in the
body is bound to TCI.

Contrary to other water-soluble vitamins, B12 can be stored in the


body for extended amounts of time, even for years. It is primarily
stored in the liver; other places are the heart, spleen, brain,
kidneys, bones, and muscles [94,93 ,49].

Function

As discussed previously, B12 plays a large part in the conversion


of homocysteine to methionine, which helps protect the heart from
disease. It assists conversion of THF into any of its coenzyme
forms, when deficient in B12, folate is trapped in its methyl form.
Cobalamin helps oxidation of several compounds. CoA and the
kreb cycle are also dependent on B12. It helps nerve cells, red
blood cells, and the manufacturing/repair of DNA. It is vital for
processing carbohydrates, proteins and fats, which help make all
of the blood cells in our bodies. It also assists memory [7,66,41].

Deficiency

Lack of B12 results in anemia, constipation, heart disease,


depression, weakness, neurological failures, permanent nerve
damage, nausea, flatulence (gas), loss of appetite, confusion,
weight loss, numbness/tingling in hands and feat, difficulty in
maintaining balance, memory loss, and soreness of the mouth or
tongue. Here is another interesting study by Petchkrua W [39]:

“Vitamin B12 (or cobalamin) deficiency is well known in


geriatric patients, but not in those with spinal cord injury
(SCI). This retrospective study describes vitamin B12
deficiency in SCI… CONCLUSION It is recommended
that physicians consider vitamin B12 deficiency in their
patients with SCI, particularly in those with neurologic
and/or psychiatric symptoms. These symptoms often
are reversible if treatment is initiated early.”

Recommendation
The DRI RDA recommends 2.4 ug of vitamin B12 per day for
adults age 19 and up. With an increase of .2 and .4ug for
pregnancy and lactation accordingly.

No toxicity has been reported for massive doses of vitamin B12.


Those with greater needs of Cobalamin are elderly people, those
with gastrointestinal disorders, vegetarians, and those with
pernicious anemia, which causes the absence of intrinsic factor,
inhibiting cyanocobalamin absorption. Great sources are meats
such as fish, shellfish, poultry, eggs (especially the yoke) and
dairy products. They are rarely contained in plants [49-52,66].

Biotin
Biotin is also known as vitamin H and coenzyme R. It was isolated
in 1936 when researchers showed consumption of raw eggs
caused a deficiency. Uncooked egg whites contain a protein
called avidin, which strongly binds to biotin in the intestinal tract
and inhibits absorption. Thankfully, cooking eggs effectively
destroys this protein. It is water soluble, and considered to be
apart of the B-complex. It is made of two rings, an ureido ring,
connected to a thiophene ring, with an additional valeric acid side
chain [63].

Digestion

Biotin connected to proteins must be digested by enzymes prior to


absorption. It is broken down to free biotin, biotoinyl peptides, or
biocytin. There is still little information concerning the absorption
of biotin in the human body. But it is believed to occur in the upper
one-third to one-half of the small intestine. Absorption within the
duodenum is thought to be higher than in the jejunum, and that is
thought to be higher than the ileum. This may occur via a sodium
dependent mechanism, or by passive diffusion. Little biotin is
absorbed in the colon. Biotin is stored in minute quantities of the
muscles, liver, and brain. Lastly, intestinal bacteria can
manufacture small amounts of biotin, making this vitamin unique
to most other vitamins, which cannot be made from natural
process [40,7].

Function

Biotin acts when covalently bound to biotin dependent enzymes


(biotin also assists cell growth and replication). These include B-
methylcrotonyl CoA carboxylase, Propionyl CoA carboxylase,
Pyruvate carboxylase, and Acetyl CoA carboxylase. We will
discuss these 4 reactions next [58,65].

B-methylcrotonyl CoA carboxylase

This enzyme is vital for the catabolism of the amino acid leucine
(the most abundant amino acid found in proteins). B-
methylcrotonyl CoA carboxylase is formed during leucine
catabolism. This is a biotin dependent reaction, and further
changed to B-methylglutaconyl CoA carboxylase, which is broken
down to form acetoacetate and acetyl CoA.

Propionyl CoA carboxylase


Propionyl CoA carboxylase is important for the breakdown of
isoleucine, threonine, and methoinine, all of which help make
propionyl CoA. Propionyl CoA carboxylase assists other
catabolization reactions. Tests show a biotin deficiency decreases
the activity of this enzyme.

Pyruvate carboxylase

A lack of biotin shows to inhibit pyruvate activity. Pyruvate


carboxylase is necessary for gluconeogenesis (synthesis of
glucose, from non-carbohydrate), and helps replenish oxalocetate
for the Krebs cycle.

Acetyl CoA carboxylase

For malonyl CoA to form Acetyl CoA carboxylase needs biotin.


This reaction provides a mechanics for digestion of several amino
acids, and chained fatty acids. Succinate formed, enters the kreb
cycle.

Jitrapakdee S and Wallace JC elaborate further on this discussion


[73]:

”The biotin carboxylase family is comprised of a group


of enzymes that utilize a covalently bound prosthetic
group, biotin, as a cofactor. These enzymes, which
include acetyl-CoA carboxylase, pyruvate carboxylase,
propionyl-CoA carboxylase, methylcrotonyl-CoA
carboxylase, geranoyl-CoA carboxylase, oxaloacetate
decarboxylase, methylmalonyl-CoA decarboxylase,
transcarboxylase and urea amidolyase, are found in
diverse biosynthetic pathways in both pro-karyotes and
eukaryotes…Further comparisons of biotin-dependent
carboxylases with other groups of enzymes in the
protein data bank reveal that this family of biotin
enzymes has strong similarities in specific domains to a
number of ATP-utilizing enzymes and to the lipoyl-
containing enzymes.”

Deficiency

Lack of this vitamin may induce hair loss, rashes around the
openings of the eyes, nose, mouth ect., central nervous system
abnormalities such as depression, lethargy, hallucinations, and
paresthesias (tingling, numbness, ect.). dermatitis, muscle pain,
loss of appetite, slight anemia, an inflamed tongue, and
weakness. Excess alcohol intake, bowel diseases, ingestion of
raw eggs, and certain drugs, will induce greater biotin needs
[114,109,66]. Furthermore, Bender DA. States [10], “Biotin
deficiency leads to impaired glucose tolerance”

Recommendation

Because of the uncertain use of biotin in the intestine, It is hard to


conclude an exact consumption rate. The 1989 RDA
recommended 30-100 mg of biotin per day for children of 11 years
of age, to adults. Another suggests is 30 ug a day for adults, and
35 ug for women. Toxicity of biotin has not been reported.
Sources for biotin are liver, brewer's yeast, egg yolk, soybeans,
peanuts, cauliflower, mushrooms, and legumes [71,72,11].

Final Recommendations

As clearly displayed, Vitamin B-complex is absolutely essential for


the bodybuilding life style. So the question is, what do you do
from here? Obtaining B-Vitamins from food is possible, but can be
very difficult, especially if you are on restricted calories. As such, I
would highly recommend you purchase a B-Complex supplement.
Furthermore, taking into account that it is virtually impossible to
consume too much of these water-soluble beasts, and that as
athletes, we are more susceptible to losing vitamins through loss
of water from animalistic training sessions, there is no reason why
you wouldn’t. But be sure to study this article thoroughly,
consume the proper servings as recommended, and avoid
harmful products such as alcohol, which promote deficiencies,
and contribute nothing but harm to your body. Finally, results
show that consuming vitamin b with a meal enhances absorption,
and avoids gastrointestinal distress, which is often induced if
consumed on an empty stomach. From there, enjoy your gains
[67,29,28,7,9].

Conclusion
20 Wisdom crieth without; she uttereth her voice in the streets:
21 She crieth in the chief place of concourse, in the openings of
the gates: in the city she uttereth her words, saying, 22 How long,
ye simple ones, will ye love simplicity? and the scorners delight in
their scorning, and fools hate knowledge? 23 Turn you at my
reproof: behold, I will pour out my spirit unto you, I will make
known my words unto you. Proverbs 1:20-23 [48]

These are exciting times my friends. The Lord Jesus has blessed
Abcbodybuilding with an abundance of innovation. My final
suggestion to our fellow hyperplasia viewers is to take advantage
of this opportunity. Knowledge is literally knocking at your door--all
you have to do is open up.

Call unto me, and I will answer


thee, and show thee great and
mighty things, which thou
knowest not. - Jeremiah 33:3
[48]
Keep it Hardcore

Venom

Venom@abcbodybuilding.com

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92. Shimakawa T, Nieto I'; Malinow M, Chambless L, Schreiner
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Table of contents
Prologue Introduction Conclusion References

Teachers’ Topics
Biochemistry of the Water Soluble Vitamins: A Lecture for First Year
Pharmacy Students
Michael G. Bartlett, PhD1
1
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy,
University of Georgia, Athens, GA 30602-2352

Keywords: biochemistry, vitamins

PROLOGUE
This manuscript describes the lecture on vitamins contained in the core course
entitled, “The Biochemical Basis of Drugs and Diseases” (Pharmacy 3050). In the
first year, our curriculum is designed to focus on systems and diseases. As such, this
course acts in concert with both the Anatomy & Physiology course and the
Pathophysiology course to present an integrated view of human diseases and
systems. The second year of our curriculum is focused on learning about drugs
classes and the mechanism of action. The third year of the curriculum is focused on
simulated patients, while the forth year of the curriculum the students are presented
with real patients.
The lecture on vitamins is the last topic of a course focused primarily on
metabolism. Because many vitamins play major roles in metabolic cycles, this
lecture allows for a brief review of much of the material covered throughout the
course. Therefore, vitamin examples are primarily chosen to reinforce major
metabolic cycles and also their role in human disease. There is more clinical
information that is relevant to vitamins than what is presented in this lecture.
However, since first year students in our curriculum have almost no knowledge of
therapeutics, the focus of the lecture is on diseases and not clinical practice.

INTRODUCTION
Vitamins are a multibillion dollar industry.1 They are readily available to the public
and are the focus of the most frequently asked questions to pharmacists.2
Surprisingly, most pharmacy students receive little training on the many roles of
vitamins in nutrition.2 Therefore, this lecture attempts to not only reinforce
fundamental biochemical and metabolic pathways in the human body, but also to
provide pharmacy students with practical information.
The diet is a vast source of important nutrients. These nutrients include several
important classes of biomolecules such as: (1) energy yielding components
(carbohydrates, lipids, and proteins), (2) essential and nonessential amino acids, (3)
essential fatty acids, (4) minerals, and (5) vitamins. Vitamins are organic substances
that must be provided by the diet either because they cannot be biosynthesized or
the amount that is provided through biosynthesis is inadequate for maintaining
normal health. Vitamins are broadly divided into 2 classes based upon their
hydrophobicity. The more hydrophilic vitamins are termed the water-soluble
vitamins and are composed of the B-complex vitamins and vitamin C. The more
hydrophobic vitamins, referred to as the fat-soluble vitamins, are composed of
Vitamins A, D, E, and K. This article focuses primarily on the water-soluble
vitamins due to their greater role in the major metabolic cycles, which are the
primary focus of this course.
The normal North American diet is sufficient to prevent significant vitamin
deficiencies and the related diseases associated with these deficiencies. However,
there is increasing concern that slight vitamin deficiencies in a number of water-
soluble vitamins (B1, B6, B12, folate and vitamin C) are risk factors for diseases
such as depression, cancer, cardiovascular disease, and neural tube defects. The
prevalence of this slight vitamin deficiency is likely related to diet, since most of
these vitamins are supplied by fruit and vegetable intake. A recent survey has shown
that only 25% of the population meets their daily intake of 5 servings.3 Food
preparation is another source of vitamin loss. For example, heating food for more
than 2 hours causes more than a 10% loss of most water-soluble vitamins.
Refrigeration, freezing, and reheating have all been shown to lead to further loss of
vitamins. Exposure to light causes significant loss of riboflavin from foods and the
combination of heating and light can almost completely remove this vitamin from
food.4
Thiamin (Vitamin B 1 )
Thiamin functions in the body as thiamin pyrophosphate (TPP) an important
enzyme co-factor.5 Thiamin reacts with adenosine triphosphate (ATP) to form
thiamin pyrophosphate through a reaction mediated by the enzyme thiamin
diphosphokinase. Following its production, TPP is incorporated into 2 important
enzymes: pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Pyruvate
dehydrogenase is part of a multi-enzyme complex that acts to convert pyruvate
generated in glycolysis into acetyl-CoA for entry into the tricarboxylic acid (TCA)
cycle. Thiamin pyrophosphate is also used as a co-factor for the enzyme α-
ketoglutarate dehydrogenase, which is a key point of regulation in the TCA cycle.
α-Ketoglutarate dehydrogenase is involved in the conversion of α-ketoglutarate to
succinyl CoA. In the case of both enzymes, TPP assists in decarboxylation of a
small ketoacid.
In addition to its uses in metabolism, thiamin may enhance circulation and blood
formation. It is required for maintenance of the nervous system and is used in the
biosynthesis of the neurotransmitters acetylcholine and γ-hydroxybutyrate (GABA).
Thiamin also is used in the production of hydrochloric acid in the stomach and,
therefore, has a role in digestion.
Thiamin is provided in the diet through most grains. A deficiency of thiamin is
called beriberi and it is most often observed in Southeast Asia.6 The main staple of
diet in this part of the world is rice, which does not provide dietary thiamin to as
great an extent as other grains. The symptoms of beriberi include limb pain, muscle
weakness, and low cardiac output. All symptoms are related to the diminished
capacity of the major energy producing pathways that are dependent on TPP as a
co-factor.
Mild deficiencies of thiamin are sometimes observed in the elderly and in low-
income groups on restricted diets. The earliest symptoms of thiamin deficiency are
loss of appetite, constipation, and nausea. Other symptoms such as mental
depression, peripheral neuropathy, irritability, and fatigue are related to the role of
thiamin in maintaining a healthy nervous system.
The most common form of thiamin deficiency in the United States is alcoholic
neuritis. Because alcoholics normally have a poor appetite, overall food
consumption is low. In addition, alcoholics are predisposed to developing
nutritional deficiencies since alcohol is their primary calorie source. Under the
broad umbrella of alcoholic neuritis come two disorders, Wernicke’s Syndrome and
Korsakoff’s Psychosis.7 The symptoms of Wernicke’s Syndrome (ophthalmoplegia,
nystagmus, and ataxia) respond quickly to administration of thiamin, whereas the
more severe memory and learning disorders associated with Korsakoff’s Psychosis
are refractory to thiamin treatment.
Riboflavin (Vitamin B 2 )
Riboflavin functions in the body as an enzyme cofactor in many oxidation/reduction
reactions and has a central role in energy production and cellular respiration.
Riboflavin reacts with ATP to form flavin mononucleotide (FMN). Flavin
mononucleotide then reacts with a second molecule of ATP to form a molecule of
flavin adenine dinucleotide (FAD). Within cellular metabolism, enzymes such as
succinyl dehydrogenase (TCA cycle), AcylCoA Dehydrogenase (β-Oxidation), and
Glycerol-3-phosphate Dehydrogenase (Glycerol Phosphate Shuttle) use FAD as a
cofactor. The enzyme NADH-CoEnzyme Q oxidoreductase (Complex I, Electron
Transport Chain) uses FMN as a co-factor. As enzyme co-factors, FAD and FMN
are able to function as electron acceptors. The addition of 2 electrons to FAD results
in the formation of a molecule of FADH2, while the addition of 2 electrons to FMN
causes the formation of a molecule of FMNH2.
Riboflavin + ATP → FMN + 2e- ↔ FMNH2
FMN + ATP → FAD + 2e- ↔ FADH2
The reduced forms of these enzyme co-factors can donate these electrons to return
to their previous fully oxidized forms. It is this ability to act as a conduit for
electron transfer reactions that makes FAD and FMN such important enzyme
cofactors.
Riboflavin is available from a wide variety of dietary sources such as milk, cheese,
meat, eggs, and cereal products. Symptoms associated with riboflavin deficiency
include sore throat, dermatitis, anemia, neuropathy, and cataract formation.
Riboflavin deficiency is not normally observed in the United States; however,
deficiency may be observed as part of a general case of malnutrition or in cases of
chronic alcoholism.8 The conversion of riboflavin to FMN is required for absorption
and transport into many tissues. The conversion has been shown to be inhibited by
hypothyroidism and the structurally similar medications chlorpromazine,
adriamycin, quinacrine, tetracycline, and tricyclic antidepressants.9-12

Niacin (Vitamin B 3 )
The vitamin niacin (nicotinic acid) and its structural analog nicotinamide have
identical function due to their facile interconversion in the body. Niacin is converted
through a series of reactions to its active form nicotinamide adenine dinucleotide
(NAD+). NAD+ can be converted to a reduced form NADH by gaining 2 electrons
through a process similar to FAD reduction. NADH is produced in large quantities
by the TCA cycle and β-Oxidation and to a lesser extent by glycolysis. Reduced
NADH is returned to its oxidized form under normal cellular conditions by the
electron transport chain. This newly reformed NAD+ can then return to other
metabolic pathways to harvest more electrons. In the body the ratio of
NAD+/NADH is approximately 1000 demonstrating the primary role of NAD+ in
supporting cellular oxidation. NADH also can react with ATP to form NADPH. As
opposed to the unphosphorylated form, the ratio of NADP+/NADPH is only 0.01.
This ratio points to the role of NADPH in supporting reductive processes in the
body.
Niacin → NAD+ + 2e- ↔ NADH
NADH + ATP ↔ NADPH + ADP
Niacin can be found in foods such as meats, breads, and beans. Mild niacin
deficiencies have similar symptoms to those observed with riboflavin, which is not
surprising due to the similar roles both of these vitamins play in biochemical
reactions. Niacin deficiencies are occasionally observed in alcoholics, cases of
general malnutrition, and in the elderly on restricted diets. A severe deficiency of
niacin is known as pellagra, which is derived from the Italian phrase meaning rough
skin. Pellagra is marked by dermatitis and also is notable for causing a blackening
of the tongue. Early cases of pellagra were first observed in Europe shortly after the
introduction of corn from the voyages of Christopher Columbus. In these cases,
poor farmers who were raising corn as animal feed were particularly susceptible.
Because niacin in corn is not bioavailable unless treated with a strong base such as
lye, the farmers developed niacin deficiencies. Europeans did not know this
processing method until revealed to them by Native-Americans during the early
colonial period of North America. However, the connection between pellagra and
niacin was not known until the early 20th century. Pellagra was a significant health
issue in the United States over the period from 1900-1940 resulting in over 100,000
deaths. Today most diets are supplemented with niacin through enriched flour,
which receives its name because of the added niacin.13
Niacin can be administered in doses of 2g to 4g to causes a decrease in circulating
levels of cholesterol and LDL. While the cholesterol lowering effects of niacin are
desirable there are potential side effects from such large doses of this vitamin. The
most immediate reaction observed from large doses of niacin is vasodilation
resulting in flushing. Over time there may be a reduction in fatty acid mobilization
causing a depletion of glycogen and lipid stores in muscle tissue. Long-term
exposure may also elevate blood glucose and uric acid levels, suggesting increased
risk for patients who are on the borderline for diseases such as diabetes and gout.
Prolonged use of high doses of niacin can lead to elevated levels of the serum
enzymes alanine aminotransferase and aspartate aminotransferase, which may
suggest liver damage.

Pyridoxine (Vitamin B 6 )
Pyridoxine is the precursor to the active enzyme co-factor pyridoxal phosphate
(PLP). Pyridoxal phosphate is a critical co-factor for enzymes involved in reactions
involving many amino acids. The N-terminus of the amino acid forms a covalent
bond to PLP, allowing a wide variety of displacement reactions to occur at the alpha
carbon. These include decarboxylations, transaminations, and transfers of side
chains. Pyridoxine, therefore, plays a central role in the production of many
neurotransmitters, such as serotonin, norepinephrine, and histamine. Pyridoxine also
is important in the production of heme.
The PLP co-factor in several enzymes is a therapeutic target due to the ability to
form irreversible covalent bonds with agents containing a hydrazine moiety, such as
carbidopa, isoniazid, and hydralazine.14 The combination of L-Dopa and carbidopa
is a widely used therapy that has a biochemical mechanism involving vitamin B6.
The conversion of L-Dopa to dopamine is catalyzed by the PLP-dependent enzyme
L-aromatic amino acid decarboxylase (LAAAD).
L-DOPA → Dopamine
The enzyme LAAAD is present in both the gut and in the brain. This presents a
problem because L-dopa is readily transported across the blood brain barrier while
dopamine is not. Therefore, orally administered L-dopa is rendered ineffective in
the gut by LAAAD. Co-administration of carbidopa resolves this dilemma by
inactivating LAAAD in the gut. Like dopamine, carbidopa cannot cross the blood
brain barrier leaving LAAAD in the brain free to carry out the production of
dopamine at the site of action. In addition to hydrazine containing drugs,
penicillamine, used in the treatment of Wilson’s disease, cystinuria, and rheumatoid
arthritis reacts with and inactivates pyridoxal phosphate.15 Patients treated with
penicillamine occasionally develop convulsions, which can be prevented by
supplementation with vitamin B6.
Pyridoxine is found in foods such as meats, breads, eggs, soybeans, and many
vegetables. A deficiency in pyridoxine can cause facial lesions, depression,
peripheral neuropathy, and glossitis. The neurological complications can be directly
linked to the effects on neurotransmitter production. Mild pyridoxine deficiencies
are sometimes observed in young women taking oral contraceptives. Deficiencies
have also been observed in patients with gasteroenteritis or Crohn’s Disease,
presumably due to poor absorption. Mild deficiencies are of concern due to a
correlation with an increased incidence of breast cancer and to the risk of coronary
heart disease.16,17 Neurotoxicity has been noted with doses of vitamin B6 in excess
of 500 mg/day.18

Cobalamin (Vitamin B 12 )
Cobalamin is vital for cell growth and replication. Its major site of action is at the
interface between the folic acid cycle and the active methyl cycle, where cobalamin
is a co-factor for the enzyme homocysteine methyltransferase. This enzyme
catalyzes the transfer of a methyl group from tetrahydrofolate to homocysteine,
forming the amino acid methionine. These 2 cycles impact many other pathways
due to the large number of methylation reactions in the body, especially nucleic acid
biosynthesis and neurotransmitter biosynthesis.
Cobalamin is found in meats and dairy products. Deficiencies are not common
because the liver can store a 6-year supply of cobalamin. In addition, cobalamin is
highly conserved by enterohepatic recirculation. Strict vegetarians (vegans) may
take up to 20 to 30 years to develop a deficiency, whereas inadequate absorption
from the ileum due to ileitis or loss of a glycoprotein that complexes with
cobalamin prior to absorption may take from 2 to 10 years to become symptomatic.
The anesthetic nitrous oxide inactivates cobalamin and can cause patients with
marginal serum levels to develop deficiencies within a week.19 While rare,
deficiencies in vitamin B12 are severe and manifest in erythrocytes and nervous
tissue. In erythrocytes, nucleic acid biosynthesis is slowed. This results in stem cells
that are committed to development into erythrocytes possessing twice their normal
protein content but lacking the necessary nuclear material for proper cell division.
The resulting anemia, termed megaloblastic anemia, can be quite severe. Cobalamin
deficiency can also cause permanent damage to the nervous system. The results are
swelling of neurons and demylination of nerve cells, followed by cell death. These
progressive manifestations cause a wide range of neurological symptoms including
unsteadiness, decreased reflexes, paresthesias of the extremities, and ultimately
confusion, memory loss, hallucinations, and psychosis. The neurological symptoms
of cobalamin deficiency may be mistaken for multiple sclerosis. In the elderly and
in alcoholics, cobalamin deficiency should be considered as a possible cause of
dementia even in the absence of anemia. The neurological symptoms associated
with cobalamin deficiency are not directly related to irregularities in the formation
of erythrocytes.20

Folic Acid (Pteroylglutamic Acid)


Folic acid is derived from the addition of a pteroyl group to the amino acid
glutamate. Folic acid can be reduced to form tetrahydrofolate, which is an important
acceptor of one-carbon units. Folic acid plays an important role in the conversion of
homocysteine to methionine by providing the methyl to the vitamin B12 dependent
methyl transferase. Therefore, folic acid levels have a strong influence on the
endogenous concentration of homocysteine. Elevated levels of homocysteine are
associated with increased risk of coronary heart disease. Supplementation with folic
acid has been shown to correct plasma homocysteine levels and decrease the
morbidity and mortality from atherosclerotic disease.21
Folic acid plays an important role in the biochemistry of amino acids; it is critical
for the interconversion of the amino acids serine and glycine and in histidine
metabolism. Folic acid also is necessary for the biosynthesis of the nucleic acids
thymidine, adenine, guanine, and inosine. Because of its role in amino acid and
nucleic acid biosynthesis, folic acid supplementation during pregnancy has been
shown to prevent most birth defects involving the brain and spinal cord, known as
neural tube defects.22
Folic acid is found in organ meats such as liver, green leafy vegetables, yeast, and
some fruits. Deficiencies in folic acid are most often observed with poor intake or
alcoholism but are sometimes seen in pregnancy where there is an increased need
for folic acid. The recommended daily allowance for pregnant women is at least
twice that for nonpregnant women.23 Folic acid deficiencies can also be observed
from reduced absorption due to diseases in the intestine. Additionally
anticonvulsants, such as phenytoin, phenobarbital, and primidone appear to not only
to inhibit folic acid absorption, but also to increase catabolism.24 There is also
concern that supplementation with folic acid may impact the effectiveness of these
anticonvulsants.
The most common effect of folic acid deficiency is megaloblastic anemia. The
appearance of this type of anemia is identical to that observed with vitamin B12
deficiency due to the common pathway shared by the folic acid and the active
methyl cycles. One major difference between folic acid deficiency and vitamin B12
deficiency is the absence of the neurological symptoms from lowered serum folic
acid levels.25

Pantothenic Acid
Pantothenic acid is one of the many B-complex vitamins. Once in the body,
pantothenic acid combines with ADP and cysteamine to form coenzyme A
(HSCoA). Coenzyme A is involved in a number of cellular pathways, most notably
in transferring an acetyl unit from the pyruvate dehydrogenase complex or from β-
oxidation to oxaloacetate in the TCA cycle. Coenzyme A is also involved in the
biosynthesis of cholesterol, steroid hormones, fatty acids, and porphyrins.
Pantothenic acid derives its name from the Greek word meaning “from
everywhere”, which reflects its ubiquitous nature in foods. Deficiencies in
pantothenic acid are difficult to achieve but result in neuromuscular degeneration.26

Biotin
Biotin is an important co-factor for enzymes involved in carboxylation reactions.
Biotin aids in these reactions by binding carbon dioxide. An important example of a
biotin-containing enzyme is pyruvate carboxylase. This enzyme catalyzes the
conversion of pyruvate to oxaloacetate as a preliminary step in gluconeogenesis.
Biotin is found in foods such as liver, egg yolks, milk, fish and nuts. Deficiencies in
biotin result in dermatitis, glossitis, muscle pain and anorexia. Deficiency in biotin
has been observed in patients ingesting raw eggs over a long period of time. Egg
white contains avidin, a protein that binds biotin, strongly preventing its absorption
from the intestine.27 Biotin deficiency was observed in early attempts at parenteral
nutrition before proper vitamin supplementation became standard practice.28
Choline
Choline has many important biochemical roles in the body. It is incorporated into
the formation of lecithin, an important structural phospholipid found most
abundantly in mitochondrial membranes. It is also incorporated into platelet-
activating factor, an important signaling agent in the clotting cascade. Choline also
affects lipid mobilization from the liver. However, its most important role is as a
precursor for the neurotransmitter acetylcholine where it plays a critical role in
motor coordination.
Choline is found in eggs, peanuts, and liver. Deficiency in choline has not been
reported in humans. It is believed that daily needs for choline can be met through
biosynthesis and diet.

Carnitine
Carnitine has an important role in the metabolism of fatty acids. Carnitine accepts
and donates fatty acids to co-enzyme A. This is an equilibrium process facilitated by
cytosolic and mitochondrial enzymes known as carnitine acyl transferases. The
attachment of fatty acids to carnitine is critical for their transport from the cytosol to
the mitochondria, where they are later metabolized through β-oxidation.
Carnitine is found abundantly in meats and dairy products. Carnitine deficiency is
not normally observed in adults unless it is caused by an inherited genetic disorder
related to its transport or biosynthesis. Carnitine deficiency causes the storage of
lipids in muscle tissue resulting in functional abnormalities in both cardiac and
skeletal muscles. However, carnitine deficiencies are not uncommon in preterm or
low birth weight infants. These infants generally respond to supplements of
carnitine as well as changing to a low-fat, high-carbohydrate diet.29

Ascorbic Acid (Vitamin C)


Ascorbic acid acts as an enzyme co-factor for 2 major biochemical processes. It is
important for many hydroxylation reactions, especially those involved in the
posttranslational hydroxylation of the amino acid proline in the formation of the
structural protein collagen. In the gut, vitamin C is involved in the reduction of iron
(III) to iron (II), allowing iron to be absorbed into the bloodstream.
Humans are one of the few organisms that are incapable of biosynthesizing ascorbic
acid. As such they are highly dependent on obtaining it from their diet. Vitamin C is
found in citrus fruits, tomatoes, strawberries, and potatoes. During the Age of
Exploration, British sailors were given the nickname “limeys” due to the barrels of
limes that were used on long voyages to supply vitamin C to the crew. The sailors
were trying to avoid a deficiency in ascorbic acid known as scurvy.30 The symptoms
of scurvy are related to inhibited synthesis of collagen. These effects include failure
of wounds to heal, defects in tooth formation, and capillary leakage. Anemia caused
from failure to adequately absorb iron is also common.31 Several factors have been
shown to lower serum vitamin C levels including smoking, oral contraceptives, and
the use of aspirin.32-34 Patients exposed to any of these conditions long-term should
consider taking a vitamin C supplement. However, the use of high doses of vitamin
C, a theory popularized by Nobel Laureate Linus Pauling, has not been shown to
provide any medical benefit.35 The use of high doses of vitamin C has been shown
to cause nausea, diarrhea, and lead to the formation of oxalate kidney stones.18, 35

Student Perception of Lecture


Student opinions were obtained using minute papers. Minute papers are given to a
group of 25-30 students following each lecture in this course.36 From the results of
the minute papers in Table 1, the student’s perception of the lecture is apparent. The
students believe that the most significant material in the lecture was the discussion
on the major biochemical functions of the vitamins. This is consistent with the
intent of the instructor. The students also felt that understanding vitamin
deficiencies and the sources of the various vitamins was important. The students
were asked what they found interesting about the lecture and not surprisingly they
selected various stories as their favorite points. They especially liked the link
between biotin, avidin, and eggs, the nautical history of scurvy resulting in the
nickname “Limeys” being given to British sailors, and understanding the role of
appetite suppression in alcoholism and general vitamin deficiencies. Over the years,
students have commented that they enjoy having interesting health related facts to
aid them in retaining and understanding the utility of biochemical information.
Vitamins provide an enormous number of examples that can be used. Finally, the
students were asked to recommend areas that could have increased focus in the
future. In general these comments fall into 2 catagories. The students are either
confused and would like more information to more fully understand the topic, or
they are genuinely interested and would like to know more. In this case, 71% of the
student responded that they did not see anything else to add. There were a few
suggestions for adding additional information on folic acid deficiency, alcoholism,
and drug-vitamin interactions. This text incorporates many of these suggestions
with the inclusion of the link between folic acid and neural tube defects, discussions
of alcoholism throughout the lecture rather than being highly focused around
thiamin, and drug interactions involving the vitamins pyridoxine, folic acid, and
riboflavin.

CONCLUSIONS
Questions concerning the use of vitamins are common. Vitamins have important
roles in many of the major metabolic pathways in the human body. In addition, drug
interactions with vitamin and diseases involving vitamin deficiencies are important
topics for pharmacy curricula. An understanding of the functional roles of vitamins
can contribute to improved understanding of general biochemistry and help
pharmacy students become better prepared for their roles as health care educators.

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Corresponding Author:
Address: Department of Pharmaceutical and Biomedical Sciences, College of
Pharmacy, University of Georgia, Athens, GA 30602-2352
Tel: (706) 542-5390
Fax: (706) 542-5358
E-mail: bartlett@rx.uga.edu
Bartlett M. Biochemistry of the Water Soluble Vitamins: A Lecture for First Year
Pharmacy Students. Am J Pharm Educ. 2003; 67(2):article 64.

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