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Abstract and Figures

Identified almost 60 years ago, pantothenic acid is an essential vitamin, which serves as the metabolic precursor for coenzyme A. In the form of coenzyme A and as a component of acyl carrier protein, pantothenic acid is a participant in a myriad of metabolic reactions involving lipids, proteins, and carbohydrates. Though essential, pantothenic acid deficiency in humans is rare owing to its ubiquitous distribution in foods of both animal and plant origin. Pantothenic acid supplementation may have some efficacy, but further investigation into various health claims is necessary before any specific recommendations can be given.
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25
Pantothenic Acid
Joshua W. Miller, Lisa M. Rogers, and Robert B. Rucker
History
The discovery of pantothenic acid followed the same
path that led to the discovery of other water-soluble
vitamins: studies utilizing bacteria and single-cell eukar-
yotic organisms (e.g., yeast), animal models, and
thoughtful chemical analysis. It was largely the efforts
of research groups associated with R.J. Williams, C.A.
Elvehjem, and T.H. Jukes that resulted in the identifica-
tion of pantothenic acid as an essential dietary factor.
Williams et al.
1
established that pantothenic acid was
required for the growth of certain bacteria and yeast.
Next, Elvehjem et al.
2
and Jukes et al.
3,4
demonstrated
that pantothenic acid was a growth and “anti-dermatitis”
factor for chickens. Williams coined the name “pantoth-
enic” acid from the Greek meaning “from everywhere”
to indicate its widespread occurrence in foodstuffs.
1,5
The eventual characterization of pantothenic acid by
Williams took advantage of observations that the anti-
dermatitis factor present in acid extracts of various food
sources (pantothenic acid) did not bind to fuller’s earth
under acidic conditions. Using chromatographic and
fractionation procedures that were typical of the 1930s
(solvent-dependent chemical partitioning), Williams
isolated several grams of pantothenic acid for structural
determination from 250 kg of liver.
5
With this informa-
tion, a number of research groups contributed to the
chemical synthesis and commercial preparation of pan-
tothenic acid.
In the 1950s, one of the functional forms of pantoth-
enic acid, coenzyme A (CoA), was discovered as the
cofactor essential for the acetylation of sulfonamides
and choline.
6
In the mid-1960s, pantothenic acid was
next identified as a component of acyl carrier protein
(ACP) in the fatty acid synthesis complex.
7
These devel-
opments, in addition to a steady series of observations
throughout this period on the effects of pantothenic
acid deficiency in humans and other animals, provided
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
the foundation for our current understanding of this
vitamin.
Chemistry and Nomenclature
The chemical structure of pantothenic acid consists of
pantoic acid and -alanine bound in amide linkage (Fig-
ure 1a). Metabolic processing of pantothenic acid, de-
scribed in detail below, produces the important interme-
diate, 4-phosphopantetheine (Figure 1b), which includes
-mercaptoethylamine (cysteamine) bound in amide
linkage to the terminal carboxyl group of the molecule.
4-Phosphopantetheine serves as a covalently linked pros-
thetic group for ACP (Figure 1c). Further metabolic pro-
cessing with the addition of adenine and ribose 3-phos-
phate produces the essential cofactor, CoA (Figure 1d).
Pure pantothenic acid is a water-soluble, viscous, yel-
low oil. It is stable at neutral pH, but is readily destroyed
by acid, alkali, and heat. Calcium pantothenate, a white,
odorless, crystalline substance, is the form of pantothenic
acid usually found in commercial vitamin supplements
due to its greater stability than the pure acid.
8
Early litera-
ture referred to pantothenic acid as chick anti-dermatitis
factor, filtrate factor, and vitamin B
3
.Today, it is often
referred to as vitamin B
5
,although the origin of this des-
ignation is obscure.
Intestinal Absorption, Plasma
Transport, and Excretion
The vast majority of pantothenic acid in food is present
as a component of CoA or 4-phosphopantetheine. To
be absorbed, these substances must first be hydrolyzed.
9
This occurs in the intestinal lumen by the sequential ac-
tivity of two hydrolases, pyrophosphatase and phospha-
tase, with pantetheine as the product. Pantetheine is
either absorbed as is, or is further metabolized to pantoth-
enic acid by a third intestinal hydrolase, pantetheinase.
2Present Knowledge in Nutrition, Ninth Edition Section V: Water-Soluble Vitamins and Related Nutrients
CCH
2
CH
2
O
HO NH C CH
OH
C
CH
3
CH
3
CH
2
OH
A. Pantothenic Acid
B. 4'-Phosphopantetheine
NH
CH
2
CH
2
HS
N
NN
N
NH
2
O
OH O
HH
HH
D. Coenzyme A
PO
2-
PO
2-
O
O
CH
2
O
CCH
2
CH
2
O
NH C CH
OH
C
CH
3
CH
3
CH
2
OPO
32-
O
NHCH
2
CH
2
HS C CH
2
CH
2
O
NH C CH
OH
C
CH
3
CH
3
CH
2
O
O
PO
32-
C. Acyl Carrier Protein
NHCH
2
CH
2
HS C CH
2
CH
2
O
NH C CH
OH
C
CH
3
CH
3
CH
2
O
O
PO
2-
PO
2-
OCH
2
CH
C
NH
O
...
...
O
Figure 1. Chemical structures of pantothenic acid, 4-phosphopantetheine, acyl carrier protein, and coenzyme A.
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
Pantothenic Acid Miller, Rogers and Rucker 3
In rats, pantothenic acid absorption was initially found
to occur in all sections of the small intestine by simple
diffusion.
9
However, subsequent work in rats and chicks
indicated that at low concentrations, the vitamin is ab-
sorbed by a saturable, sodium-dependent transport mech-
anism.
10
Moreover, it has been demonstrated that pan-
tothenic acid shares a common membrane transport
system in the small intestine with another vitamin, biotin.
In vitro experiments utilizing Caco-2 cell mono-layers as
amodel of intestinal absorption established that pantoth-
enic acid uptake is inhibited competitively by biotin and
vice versa.
11
Similar observations have been made in
transport experiments involving the blood-brain barrier,
12
heart,
13
and placenta.
14
After absorption, pantothenic
acid enters the circulation, where it is taken up by cells
in a manner similar to that of intestinal absorption (see
below). The vitamin is excreted in the urine primarily as
pantothenic acid. This occurs after its release from CoA
by a series of hydrolysis reactions that cleave off the phos-
phate and -mercaptoethylamine moieties.
Pantothenic Acid
4'
4'-Phosphopantothenoylcysteine
4'-Phosphopantetheine
4'-Dephospho-Coenzyme A
Coenzyme A
ATP
ADP
CTP + Cysteine
CDP + P
i
CO
2
ATP
PP
i
ATP
ADP
4'-Phosphopantothenoylcysteine
Decarboxylase
Dephospho-CoA
Pyrophosphorylase
Dephospho-CoA
Kinase
Inhibited by CoA and
CoA derivatives
Inhibition reversed b
y
carnitine
3', 5'- ADP
CoA Hydrolase
Pantothenic Acid
4'-Phosphopantothenic Acid
4'-Phosphopantetheine
4'-Dephospho-Coenzyme A
Coenzyme A
ATP
ADP
CTP + Cysteine
CDP + P
i
CDP + P
i
CO
2
CO
2
ATP
PP
i
PP
i
ATP
ADP
Pantothenic Acid
Kinase
4'-Phosphopantothenoylcysteine
Synthetase
4'-Phosphopantothenoylcysteine
Decarboxylase
4'-Phosphopantothenoylcysteine
Decarboxylase
Dephospho-CoA
Pyrophosphorylase
Dephospho-CoA
Pyrophosphorylase
Dephospho-CoA
Kinase
Dephospho-CoA
Kinase
Inhibited by CoA and
CoA derivatives
Inhibited by CoA and
CoA derivatives
Inhibition reversed b
y
carnitine
Inhibition reversed b
y
carnitine
3', 5'- ADP
CoA Hydrolase
Figure 2. Metabolic conversion of pantothenic acid to coenzyme A.
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
Functions and Cellular Regulation
Coenzyme A and Acyl Carrier Protein
Synthesis
Pantothenic acid is nutritionally essential due to the
inability of animal cells to synthesize the pantoic acid
moiety of the vitamin. The primary function of pantoth-
enic acid is to serve as substrate for the synthesis of CoA
and ACP (Figure 2). The first step is the phosphorylation
of pantothenic acid to 4-phosphopantothenic acid by
pantothenic acid kinase.
15,16
The kinase possesses a broad
pH optimum (between 6 and 9) with a K
m
for pantothenic
acid of about 20 M. Mg-ATP is used as the nucleotide
substrate for this phosphorylation reaction with a K
m
of
about 0.6 mM.
The pantothenic acid kinase reaction also serves as the
primary control point in the synthesis of CoA and ACP.
The reaction is activated and inhibited nonspecifically by
various anions. More significantly, feedback inhibition of
the kinase by CoA or CoA derivatives governs flux
4Present Knowledge in Nutrition, Ninth Edition Section V: Water-Soluble Vitamins and Related Nutrients
through the subsequent steps in the CoA synthesis path-
way and defines the upper threshold for intracellular CoA
cofactor levels. Inhibition by acetyl-CoA is slightly
greater than that of free CoA. The inhibition by free CoA
is uncompetitive with respect to pantothenate concentra-
tion, with a K
i
for inhibition of 0.2 M.
L-carnitine, which is important for the transport of
fatty acids into mitochondria, is a nonessential activator
of pantothenic acid kinase. Carnitine has no effect by
itself, but specifically reverses the inhibition by CoA. In
heart tissue, the free carnitine content varies directly with
the phosphorylation of pantothenic acid. Thus, these
properties of the kinase provide a potential mechanism
for the control of CoA synthesis and the regulation of
cellular pantothenic acid content: feedback inhibition by
CoA and its acyl esters that is reversed by changes in the
concentration of free carnitine. However, it is important
to underscore that the free concentration of acyl CoA in
cells is low and variable, because the bulk of acyl deriva-
tives are protein bound. Moreover, similar to CoA, carni-
tine exists in both free and acylated forms, and reversal of
kinase inhibition by CoA does not occur when carnitine is
acylated.
15
The ratio of free to acylated carnitine varies
considerably depending on feeding and hormonal influ-
ences, with insulin being particularly important. Fasting
and diabetes (states of low insulin) increase pantothenic
acid kinase activity and the total content of CoA.
17-19
In
addition, the perfusion of heart preparations or incuba-
tion of liver cells with glucose, pyruvate, or palmitate
markedly inhibits pantothenic acid phosphorylation, due
to reduction in free carnitine and increases in the free and
acylated forms of CoA.
Following 4-phosphopantothenic acid formation, the
subsequent steps in CoA synthesis are carried out on a
protein complex (approximately 400,000 Da) with multi-
functional catalytic sites. Important enzymatic features of
this complex include dephospho-CoA-pyrophosphory-
lase activity, which catalyzes the reaction between 4-pho-
Table 1. Selected Functions of Coenzyme A (CoA) and Acyl Carrier Protein (ACP)
Function Importance
Carbohydrate-Related Oxidative metabolism
Citric acid cycle transfer reactions Production of carbohydrates important to cell structure
Acetylation of sugars (e.g. N-acetylglucosamine)
Lipid-Related
Phospholipid biosynthesis Cell membrane formation and structure
Isoprenoid biosynthesis Cholesterol and bile salt production
Steroid biosynthesis Steroid hormone production
Fatty acid elongation, acyl (fatty acid) and triacyl Ability to modify cell membrane fluidity
glyceride synthesis Energy storage
Protein-related Altered protein conformation; activation of certain
Protein acetylation hormones and enzymes (e.g., adrenocoriticotropin);
transcription (e.g., acetylation of histone)
Protein acylation (myristic and palmitic acid additions) and Compartmentalization and activation of hormones and
prenylation transcription factors
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
sphopantetheine and ATP to form 4-dephospho-CoA;
dephospho-CoA-kinase activity, which catalyzes the
ATP-dependent final step in CoA synthesis; and CoA
hydrolase activity, which catalyzes the hydrolysis of CoA
to 3,5-ADP and 4-phosphopantetheine. This sequence
of reactions is referred to as the CoA/4-phosphopanteth-
eine cycle, and it provides a mechanism by which the
4-phosphopantetheine can be recycled to form CoA.
Each turn of the cycle utilizes two molecules of ATP and
produces one molecule of ADP, one molecule of pyro-
phosphate, and one molecule of 3,5-ADP (Figure 2).
20
ACP is sometimes referred to as a “macro-cofactor,”
because in bacteria, yeast, and plants, it is composed of
apolypeptide chain (mol. wt of approximately 8500– 8700
Da) to which 4-phosphopantetheine is attached. How-
ever, in higher animals, ACP is most often associated
with a fatty acid synthase complex that is composed of
two very large protein subunits (mol. wt. about 250,000
Da each). The carrier segment or domain of the fatty acid
synthetic complex is also called the ACP, one of seven
functional or catalytic domains on each of the two sub-
units that comprise fatty acid synthase. The inactive ACP
apopolypeptide (or domain) is converted to an active ho-
loform (or domain) by the post-translational transfer of
a4-phosphopantetheinyl moiety to the side-chain hy-
droxyl of a serine residue at the active center of ACP.
The reaction is catalyzed by 4-phosphopantetheinyl
transferase, which uses CoA as the 4-phosphopanteth-
eine substrate. Although there are few data related to the
regulation of holo-ACP peptide or domain formation,
the 4-phosphopantetheine transferase gene recently has
been cloned from a human source.
21
Selected Functions of CoA and ACP
Important functions of CoA and ACP are listed in
Table 1. Principally, CoA is involved in acetyl and acyl
transfer reactions and processes related to oxidative me-
tabolism and catabolism, whereas ACP is involved pri-
Pantothenic Acid Miller, Rogers and Rucker 5
marily in synthetic reactions. The adenosyl moiety of
CoA provides a site for tight binding to CoA-requiring
enzymes, while allowing the phosphopantetheine portion
to serve as a flexible arm to move substrates from one
catalytic center to another. Similarly, when pantothenic
acid (as 4-phosphopantetheine) in ACP is used in the
transfer reactions associated with the fatty acid synthase
process, 4-phosphopantetheine also functions as a flexi-
ble arm that allows for an orderly and systematic presenta-
tion of acyl derivatives to each of the active centers of the
fatty acid synthase complex. A summary of catalytic sites
and their functions in the fatty acid synthase complex is
presented in Table 2.
In addition to fatty acid synthesis, hints that ACP-
like factors may perform other functions in humans and
animals come from observations that an oligosaccharide-
linked ACP acts as a transmethylation inhibitor in por-
cine liver.
22
ACP is also structurally homologous to acidic
ribosomal structural proteins, such as ribosomal protein
P2.
23
Moreover, in bacteria and plants, ACP is important
in a number of pathways, such as amino acid synthesis
and the formation of polyketides, a remarkably diverse
group of secondary metabolites that include antibiotics
such as erythromycin, cholesterol-lowering drugs such as
lovastatin, and putative anti-aging compounds such as
resveratrol.
24
Table 2. Catalytic Sites Associated with the Fatty Acid Synthase Complex
Step Action(s)
1. Acetyl transferase Catalyzes the transfer of an activated acetyl group on CoA to the sulfidryl group
of 4-phosphopantetheine (ACP domain); in a subsequent step, the acetyl
group is transferred to a second cysteine-derived sulfidryl group near active
site of 3-oxoacyl synthase (see step 3) leaving the 4-phosphopantetheine
sulfidryl group free for Step 2
2. Malonyl transferase This enzyme catalyzes the transfer of successive in-coming malonyl groups to 4-
phosphopantetheine
3. 3-Oxoacyl synthetase The first condensation reaction in the process, catalyzed by 3-oxoacyl synthase,
in which attack on malonyl-ACP by the acetyl moiety (transferred in Step 1)
occurs with decarboxylation and condensation to yield a 3-oxobutryl
(acetoacetyl) derivative; in the second through the seventh cycles, it is the
newly formed acyl moieties that attacks the malonyl group added at each cycle
(see Step 6)
4. Oxoacyl reductase Reductions of acetoacetyl or 3 oxoacyl intermediates involve NADPH; the first
cycle of this reaction generates D-hydroxybutyrate, and in subsequent cycles,
hydroxyfatty acids
5. 3-Hydroxyacyl dehydratase This enzyme catalyzes the removal of a molecule of water from the 3-hydroxyacyl
derivatives produced in Step 4 to form enoyl derivatives
6. Enoyl reductase Reduction of the enoyl derivatives (Step 5) by a second molecule of NADPH
generates a fatty acid; this acyl group is also transferred to the sulfidryl group
adjacent to 3-oxoacyl synthase, as described in step 1, until a 16-carbon
paimitoyl group is formed; this group, still attached to the 4-phosphopante-
theine arm, is highly specific substrate for the remaining enzyme of the
complex, thioester hydrolase
7. Thioester hydrolase This enzyme liberates palmitic acid (Step 6) from the 4-phosphopantetheine arm
ACP acyl carrier protein; CoA coenzyme A.
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
It is also important to appreciate that intermediates
arising from the transfer reactions catalyzed by CoA and
4-phosphopantetheine in ACP may be viewed as “high-
energy” compounds. CoA or ACP reacts with acetyl
or acyl groups to form thioesters. Thioesters (MSM
COMR) are thermodynamically less stable than typical
esters (MOMCOMR) or amides (MNMCOMR). The
double-bond character of the CMObond in
MSMCOMRdoes not extend significantly into the
CMSbond. This causes thioesters to have relatively a
high energy potential, and for most reactions involving
CoA or ACP, no additional energy (e.g., from ATP hy-
drolysis) is required for transfer of the acetyl or acyl group.
For example, at pH 7.0, the Gofhydrolysis is about
7.5 kcal for acetyl-CoA and 10.5 kcal for acetoacetyl-
CoA compared with 7 to 8 kcal for the hydrolysis of ATP
to AMP and pyrophosphate or ADP and phosphate. The
terminal thiol group of CoA and ACP is also ideally
suited for nucleophilic substitution reactions involving ac-
tivated carboxylic acids and -and -carbonyl func-
tions.
25
Cellular Regulation of Pantothenic Acid and
CoA Levels
As noted above, both biotin and pantothenic acid ap-
pear to share the same transporters for cellular uptake and
6Present Knowledge in Nutrition, Ninth Edition Section V: Water-Soluble Vitamins and Related Nutrients
perhaps efflux.
11
Whether it is an intestinal, hepatic, or
cardiac muscle cell, the process for pantothenic acid cellu-
lar uptake appears saturable, with an apparent K
m
of 15
to 20 M. Transport across cell membranes appears to
occur by carrier-mediated, sodium gradient-dependent,
and electroneutral mechanisms.
13,26-29
Pantothenic acid
cellular uptake has also been linked to protein kinase C
and calmodulin-dependent regulatory and signaling path-
ways.
27
The dependence on protein kinase C is based
on observations that pretreatment of cells with a protein
kinase C activator such as phorbol 12-myristate 13-ace-
tate or 1,2-dioctanoyl-glycerol significantly inhibits pan-
tothenic acid uptake. If an inward sodium gradient is im-
posed, a rapid uptake of pantothenic acid is observed.
Uptake of pantothenic acid is reduced when sodium is
replaced by potassium or if external sodium is reduced
below 40 mM. Ouabain, gramicidin D, cyanide, azide,
and 2,4-dinitrophenol also act as inhibitors.
With regard to efflux, unlike uptake, the export of
pantothenic acid is unaffected by the addition of pantoth-
enic acid, sodium, ouabain, gramicidin D, or 2,4-dinitro-
phenol to the external medium. Moreover, the metabolic
state also has an impact on uptake. For example, in the
perfused heart, pantothenic acid transport is significantly
increased when hearts are perfused and are acting as
“working” hearts because of addition of a fuel source.
27
That active uptake of pantothenic acid is underscored
by the differences in cellular versus plasma concentrations
of free pantothenic acid. The cellular concentration of
free pantothenic acid in the liver is 10 to 15 Mand in
the heart about 100 M, compared with 1 to 5 Mob-
served in plasma. Similarly, the unidirectional influx of
pantothenic acid across cerebral capillaries (the blood-
brain barrier) occurs by a low-capacity, saturable transport
system with a half-saturation concentration approxi-
mately 10 times the plasma pantothenic acid concentra-
tion.
30,31
For comparison, the concentrations of CoA and
ACP are 50 to 100 Mand 10 M, respectively, in the
cytosol of typical cells. In mitochondria, the CoA concen-
tration can be as much as 10- to 20-fold higher, or 70%
to 90%of the total cellular CoA content.
In addition to cellular transport, enzymes associated
with CoA synthesis also have significant impact on main-
taining cellular levels of pantothenic acid and related
compounds. As described above, the most important of
these enzymes is pantothenic acid kinase.
15
Dietary Sources and Requirements
Pantothenic acid is found in a wide variety of foods
of both plant and animal origin at levels ranging from 20
to 50 g/g. Particularly rich sources of pantothenic acid
include chicken, beef, liver and other organ meats, whole
grains, potatoes, and tomato products.
32
Royal bee jelly
and ovaries of tuna and cod also have high levels of the
vitamin.
33
Because of its thermal lability and susceptibility
to oxidation, significant amounts of pantothenic acid are
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
lost from highly processed foods, including refined grains
and cooked or canned meats and vegetables. Processing
and refining whole grains results in a 37%to 47%loss
of pantothenic acid, while canning of meats, fish, and
dairy products leads to losses of 20%to 35%.
34
Greater
losses of the vitamin occur during canning (46%–78%)
and freezing (37%–57%)ofvegetables. Pantothenic acid
is also synthesized by intestinal microorganisms,
35
al-
though the amount produced and the availability of the
vitamin from this source is unknown.
The primary source of pantothenic acid in food is
CoA. Intestinal phosphatases and nucleosidases are capa-
ble of very efficient hydrolysis of CoA so that near-quan-
titative release of pantothenic acid occurs as a normal part
of digestion. Further, the overall K
m
for pantothenic acid
intestinal uptake is 10 to 20 M. At an intake of about
10 to 15 mg of CoA, the amount of CoA in a typical
meal, the pantothenic acid concentration in luminal fluid
would be about 1 to 2 M. At this concentration, pan-
tothenic acid would not saturate the transport system,
and as a consequence, should be efficiently and actively
absorbed.
11
Adietary reference intake has yet to be established for
pantothenic acid. Adequate intakes (AIs) for men and
women throughout the life cycle have been suggested
based on observed mean intakes and estimates of basal
excretion in urine (Table 3).
36
Urinary excretion of pan-
tothenic acid only exceeds basal levels when intakes are
Table 3. Adequate Intakes (AIs) for Pantothenic
Acid (From Food and Nutrition Board, Institute of
Medicine. Dietary Reference Intakes for Thiamin,
Riboflavin, Niacin, Vitamin B6, Folate, Vitamin
B12, Pantothenic Acid, Biotin, and Choline.
Washington, DC: National Academies Press;
1998. Available online at: http://www.nap.edu/
openbook/0309065542/html/)
Age Group AI (mg/d)
Infants
0–5 months 1.7
6–12months 1.8
Children
1–3 years 2.0
4–8 years 3.0
9–13 years 4.0
Adolescents
14–18 years 5.0
Adults
19–50 years 5.0
50 years 5.0
Pregnant women 6.0
Lactating women 7.0
Pantothenic Acid Miller, Rogers and Rucker 7
greater than 4 mg/d in young adult males. Thus, an intake
of 4 mg/d likely reflects the level at which saturation of
the body pool occurs.
37
Estimates of dietary intake in
healthy adults have ranged from 4 to 7 mg/d.
37-40
There
is no evidence to suggest that this range of intake is inade-
quate, and 5 mg/d has been set as the AI for adults. For
those older than 51 years, the AI remains the same, as
there is currently no basis for expecting an increased re-
quirement in elderly individuals. During pregnancy, the
AI is increased to 6 mg/d based on usual intakes of 5.3
mg/d
41
with rounding up. During lactation, the AI is
increased further to 7 mg/d, accounting for additional
secretion of the vitamin in human milk (1.7 mg/d) and
the lower maternal blood concentrations reported when
intakes are about 5 to 6 mg/d.
41-43
This is likely the result
of efficient sequestering of the vitamin in human milk,
estimated to be 0.4 mg for every 1 mg of pantothenic
acid consumed during active lactation.
44
The AI for infants reflects the mean intake of infants
fed principally with human milk, which contains about
5to6mgofpantothenic acid per 1000 kcal. Values for
children and adolescents have largely been extrapolated
from adult values. These values are supported by studies
comparing intake and urinary excretion of the vitamin in
preschool children.
45
Dietary intake of pantothenic acid
was 3.8 and 5 mg/d in children of high and low socioeco-
nomic status, respectively, and urinary excretion was 3.36
and 1.74 mg/d, respectively. In a separate study, 35
healthy girls 7 to 9 years of age were fed defined diets
and urinary excretion was measured.
46
The average daily
excretion was 1.3 mg/d when intake was 2.79 mg/d, and
2.7 mg/d when intake was 4.45 mg/d. Therefore, intakes
of 2.8 to 4.5 mg/d exceed urinary excretion of the vitamin.
In healthy adolescents (13–19 years of age), 4-day diet
records indicated that the average pantothenic acid intake
was 6.3 mg/d for males and 4.1 mg/d for females.
47
The
average urinary excretion in this latter study was 3.3 and
4.5 mg/d for males and females, respectively, while whole
blood pantothenic acid concentrations averaged 1.86
Table 4. Effects of Pantothenic Acid Deficiency in Selected Species
Species Symptoms
Chicken Dermatitis around beak, feet, and eyes; poor feathering; spinal cord myelin degeneration;
involution of the thymus; fatty degeneration of the liver
2-4,49-51
Rat Dermatitis; loss of hair color; loss of hair around the eyes; hemorrhagic necrosis of the adrenals;
duodenal ulcer; spastic gait; anemia; leukopenia; impaired antibody production; gonadal atrophy
with infertility
52-56
Dog Anorexia; diarrhea; acute encephalopathy; coma; hypoglycemia; leukocytosis; hyperammonemia;
hyperlactemia; hepatic steatosis; mitochondrial enlargement
57,58
Pig Dermatitis; hair loss; diarrhea with impaired sodium, potassium, and glucose absorption;
lachrymation; ulcerative colitis; spinal cord and peripheral nerve lesions with spastic gait
59,60
Human Numbness and burning of feet and hands; headache; fatigue; insomnia; anorexia with gastric
disturbances; increased sensitivity to insulin; decreased eosinopenic response to
adrenocorticotropic hormone; impaired antibody production
61-63
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
mol/L and 1.57 mol/L, respectively. Normal blood
concentrations of the vitamin in healthy individuals have
been reported to range from 1.6 to 2.7 mol/L.
48
Taken
together, these data indicate that intakes of 4 mg/d is
sufficient to maintain normal blood concentrations in ad-
olescents.
Using the estimate of 20 to 50 gpantothenic acid per
gram typically found in edible animal and plant tissues, it
is possible to meet the AI for adults with a mixed diet
containing as little as 100 to 200 g of solid food, the
equivalent of a mixed diet corresponding to 600 to 1200
kcal or 2.4 to 4.8 MJ. The typical Western diet contains
6mgormore of available pantothenic acid.
37
For a more
detailed review of the AIs for pantothenic acid, see the
Dietary Reference Intakes report from the Institute of
Medicine.
36
Deficiency and Toxicity
The essentiality of pantothenic acid has been docu-
mented in a wide variety of animal species. The classical
signs of deficiency, first recognized by Elvehjem, Jukes,
and colleagues
4-6
in chickens, include growth retardation
and dermatitis. Many other physiological systems are af-
fected by pantothenic acid deficiency, owing to the diver-
sity of metabolic functions in which CoA and ACP par-
ticipate. Neurological, immunological, hematological,
reproductive, and gastrointestinal pathologies have been
reported. The effects of pantothenic acid deficiency in
different species are summarized in Table 4.
49-63
Assuming that the human adult requirement for pan-
tothenic acid is about 5 mg/d, it may be predicted that
with a severe dietary deficiency, 5 to 6 weeks would be
required before clear signs of deficiency are observed. This
is based on the estimate that daily excretion of 5 mg repre-
sents a 1%to 2%loss of the total body pool of pantothenic
acid. Consistent with this estimate, limited studies in hu-
mans indicate that about 6 weeks of severe depletion are
8Present Knowledge in Nutrition, Ninth Edition Section V: Water-Soluble Vitamins and Related Nutrients
required before urinary pantothenic acid decreases to a
basal level of excretion.
64-66
Because pantothenic acid is such a ubiquitous compo-
nent of foods, both animal and vegetable, deficiency in
humans is very rare. If present, pantothenic acid defi-
ciency is usually associated with multiple nutrient defi-
ciencies, thus making it difficult to discern effects specific
to a lack of pantothenic acid. What is known about pan-
tothenic acid deficiency in humans comes primarily from
two sources of information. First, during World War II,
malnourished prisoners of war in Japan, Burma, and the
Philippines experienced numbness and burning sensa-
tions in their feet. While these individuals suffered multi-
ple deficiencies, this specific syndrome was only reversed
upon pantothenic acid supplementation.
61
Second, exper-
imental pantothenic acid deficiency has been induced in
both animals and humans by the administration of the
pantothenic acid kinase inhibitor -methylpantothenate,
in combination with a diet low in pantothenic acid.
62,63,67
Observed symptoms in humans included numbness and
burning of the hands and feet similar to that experienced
by the World War II prisoners of war, as well as a myriad
of other symptoms listed in Table 4. Some of the same
symptoms are produced when individuals are fed a semi-
synthetic diet from which pantothenic acid has been es-
sentially eliminated, but without the addition of -meth-
ylpantothenate.
64
Another pantothenic acid antagonist,
calcium hopantenate, has been shown to induce encepha-
lopathy with hepatic steatosis and a Reye’s-like syndrome
in both dogs and humans.
68,69
Oral pantothenic acid,
even in doses as high as 10 to 20 g/d, is well tolerated
70,71
;
however, occasional mild diarrhea may occur.
Status Determination
Pantothenic acid status is reflected by both whole-
blood concentration and urinary excretion. As cited
above, whole-blood concentrations typically range from
1.6 to2.7mol/L,
48
and a value under 1 mol/L is con-
sidered low. Urinary excretion is considered a more relia-
ble indicator of status because it is more closely related
to dietary intake.
37,47,62-64
Excretion of less than 1 mg of
pantothenic acid per day in urine is considered low.
Plasma level of the vitamin is a poor indicator of status
because it is not highly correlated with changes in intake
or status.
43,72
Pantothenic acid concentrations in whole blood,
plasma, and urine are measured by microbiological assay
employing Lactobacillus plantarum.For whole blood, en-
zyme pretreatment is required to convert CoA to free
pantothenic acid because L. plantarum does not respond
to CoA. Other methods that have been employed to as-
sess pantothenic acid status include radioimmunoassay,
enzyme-linked immunosorbent assay, and gas chroma-
tography. The topic of pantothenic acid status assessment
has been reviewed previously.
72
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
Health Claims
With the rapid development of the Web, information
about dietary supplements and their putative health bene-
fits can be and is disseminated to the general public with
an ease and pace never before possible. However, many
health claims for dietary supplements have little or no
scientific basis. Although overt deficiency of pantothenic
acid is extremely rare in humans, a Web search for “pan-
tothenic acid” reveals numerous websites providing back-
ground information, health claims, and, of course, an op-
portunity to buy the vitamin for oral consumption. Some
of the claims made on these websites are completely un-
warranted. For example, the use of pantothenic acid to
prevent and treat graying hair was based on the observa-
tion that pantothenic acid deficiency in rodents causes
their fur to turn gray.
53
No association between graying
of hair in humans and pantothenic acid status has ever
been demonstrated. In contrast, some claims for pantoth-
enic acid have a more credible scientific basis and are
worthy of review.
Cholesterol Lowering
Pantothenic acid is not particularly effective in lower-
ing serum cholesterol levels. Rather, oral doses of its me-
tabolite, pantetheine, or more specifically the dimer, pan-
tethine, induce favorable effects on serum cholesterol
concentrations. Several studies have indicated that pan-
tethine, in doses typically ranging from 500 to 1200 mg/d,
can lower total serum cholesterol, low-density lipoprotein
cholesterol, and triacylglycerols, and raise high-density
lipoprotein cholesterol in individuals with dyslipidemia,
hypercholesterolemia, and hyperlipoproteinemia associ-
ated with diabetes.
73-78
The effects are very favorable
compared with those of the more conventional lipid-low-
ering drugs, such as lovastatin, which tend to be associated
with significant side effects and potential liver toxicity.
In contrast, there appear to be no adverse effects associ-
ated with high-dose pantethine therapy. Furthermore,
evidence exists that pantethine therapy is more effective
than dietary modification in reducing serum cholesterol
and lipid concentrations.
73
The mechanism by which
pantethine exerts its hypolipemic effects is unclear. A hy-
pothesized site of action is in the regulation of liver sterol
biosynthesis. Because pantethine is a coenzyme precursor,
it may shunt active acetate from sterol synthesis to mito-
chondrial oxidative and respiratory pathways.
79
Addition-
ally, pantethine may promote improved triacylglycerol
and low-density lipoprotein cholesterol catabolism, as
well as reduced cholesterol synthesis via inhibition of the
enzyme hydroxymethyl glutaryl-CoA-reductase.
80-82
Enhancement of Athletic Performance
Scientific support for an effect of pantothenic acid sup-
plements on athletic performance is limited. Until re-
cently, most of the potential benefit has been inferred
from animal studies. More than 60 years ago, frog muscles
soaked in pantothenic acid solution were shown to do
Pantothenic Acid Miller, Rogers and Rucker 9
twice as much work as control muscles before giving
out,
83
and more than 30 years ago, rats supplemented
with high doses of pantothenic acid were shown to with-
stand exposure to cold water longer than unsupplemented
rats.
84
Moreover, rats deficient in pantothenic acid be-
came exhausted more rapidly during exercise than did
replete controls.
85
In this latter study, deficiency was asso-
ciated with lower tissue CoA concentrations and greater
depletion of glycogen reserves during exercise.
Studies assessing the influence of pantothenic acid on
human performance are mixed. In one study, well-trained
distance runners were supplemented with 2 g/d of pan-
tothenic acid for 2 weeks.
86
These athletes outperformed
other equally well-trained distance runners who received
placebo. Those who received the supplements also used
8%less oxygen to perform equivalent work and had about
17%less lactic acid accumulation. These differences, par-
ticularly in the context of athletic competition, are poten-
tially significant. However, in a separate study, no effect
on performance was observed in highly conditioned dis-
tance runners after receiving 1 g/d of pantothenic acid
for 2 weeks.
87
Additionally, no difference in performance
was observed among highly trained cyclists given either a
combination of thiamin (1 g) and pantethine/pantothenic
acid (1.9 g) or placebo. The supplement or placebo was
given for 7 days before each exercise test. The investiga-
tors found no effect on any physiological or performance
parameters during steady-state or high-intensity exer-
cise.
88
Further research is warranted in this area, including
investigation into whether performance can be enhanced
for average individuals, as well as elite athletes working
at the limits of human performance.
Rheumatoid Arthritis
Over 50 years ago, researchers noted that young rats
made acutely deficient in pantothenic acid suffered de-
fects in growth and development of bone and cartilage
that were reversed by repletion of the vitamin.
89
Subse-
quently, blood levels of pantothenic acid in humans with
rheumatoid arthritis were found to be lower than in
healthy controls. On the basis of this finding, an un-
blinded trial was conducted in which 20 patients with
rheumatoid arthritis were injected daily with 50 mg of
calcium pantothenate.
90
Blood levels of pantothenic acid
increased to normal, and relief from rheumatoid symp-
toms was achieved in most cases. Symptoms recurred
when supplementation was discontinued. Similar results
were obtained in arthritic vegetarians.
90
In 1980, it was
reported in a double-blind, placebo trial that oral doses
of calcium pantothenate (2g/d) reduced the duration
of morning stiffness, degree of disability, and severity of
pain in patients with rheumatoid arthritis.
91
Individuals
with other forms of arthritis were not helped by the sup-
plements, indicating that a therapeutic effect of pantoth-
enic acid may be specific for rheumatoid arthritis. No
other published studies are available to confirm this po-
tential benefit.
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
Wound Healing
Oral administration of pantothenic acid and applica-
tion of pantothenol ointment to the skin have been shown
to accelerate the closure of skin wounds and increase the
strength of scar tissue in animals. Adding calcium
D-pantothenate to cultured human skin cells given an
artificial wound increased the number of skin cells and
the distance that they migrated across the edge of the
wound.
92
These effects are likely to accelerate wound
healing. Little in vivo data, however, exist for humans to
support the findings of accelerated wound healing in cell
culture and animal studies. A randomized, double-blind
study examining the effect of supplementing patients
undergoing surgery for tattoo removal with 1000 mg of
vitamin C and 200 mg of pantothenic acid did not dem-
onstrate any significant improvement in the wound heal-
ing process in those who received the supplements.
93
Fur-
thermore, no benefits were observed when the doses were
increased to 3000 mg of ascorbic acid and 900 mg of
pantothenic acid.
94
Atopical form of pantothenic acid,
panthenol or dexapanthenol, appears to play some role in
the management of minor skin disorders. Dexapanthenol
may help maintain skin hydration in cases of radiation
dermatitis,
95
afrequent side effect of radiation therapy
for cancer, and may reduce skin irritation caused by exper-
imental sodium lauryl sulfate exposure.
96
Dexpanthenol
has also been recommended to treat cheilitis (chapped
lips) and dry nasal mucosa associated with treatment with
the acne drug isotretinoin.
97
Lupus Erythematosus
It has been hypothesized by Leung
98
that lupus erythe-
matosus, a systemic autoimmune disorder that affects the
skin, joints, and various internal organ systems, may be
the result of pantothenic acid deficiency. The hypothesis
is based on the supposition that pantothenic acid defi-
ciency may be induced by three drugs— procainamide,
hydralazine, and isoniazid—that are also known to cause
drug-induced lupus erythematosus. These drugs are me-
tabolized via CoA-dependent acetylation, and the in-
creased demand for CoA may cause pantothenic acid de-
ficiency. However, no data have been generated on the
effect of these drugs on cellular CoA or pantothenic acid
concentrations. Leung further postulated that non-drug-
induced systemic lupus erythematosus may be the conse-
quence of an increased need for pantothenic acid in sus-
ceptible individuals with genetic polymorphisms in CoA-
dependent enzymes.
98
Such polymorphisms remain to be
identified. Nonetheless, Leung recommended that lupus
erythematosus be treated with a combination of vitamins
and minerals, including 10 g/d of pantothenic acid.
98
Support for such pharmacological doses comes from
studies carried out in the 1950s. Some, but not all, symp-
toms of lupus erythematosus were alleviated with high
doses (8–15 g/d) of pantothenic acid derivatives (calcium
pantothenate, panthenol, or sodium pantothenate)
alone
99
or in combination with vitamin E supple-
10 Present Knowledge in Nutrition, Ninth Edition Section V: Water-Soluble Vitamins and Related Nutrients
ments.
100,101
No improvements in disease symptoms were
observed with lower doses (400–600 mg) of calcium pan-
tothenate.
102
With modern technology available to probe
genes for polymorphic variability, studies in lupus erythe-
matosus patients should be repeated to test the hypothesis
that a genetic-based increased requirement of pantoth-
enic acid underlies the pathogenesis of this disease.
Summary and Future Directions
Identified almost 60 years ago, pantothenic acid is an
essential vitamin that serves as the metabolic precursor
for CoA. In the form of CoA and as a component of
ACP, pantothenic acid is a participant in a myriad of
metabolic reactions involving lipids, proteins, and carbo-
hydrates. Though essential, pantothenic acid deficiency
in humans is rare due to its ubiquitous distribution in
foods of both animal and plant origin. Pantothenic acid
supplementation above and beyond adequate dietary in-
takes may be beneficial for such purposes as cholesterol
lowering, enhanced athletic performance, relief from the
symptoms of rheumatoid arthritis and lupus erythemato-
sus, and wound healing, but further investigation into
these and other health claims is necessary.
References
1. Williams RJ, Lyman CM, Goodyear GH, Trues-
dail JH, Holaday D. “Pantothenic acid”, a growth
determinant of universal biological occurrence. J
Am Chem Soc. 1933;55:2912–2927.
2. Wooley DA, Waisman HA, Elvehjem CA. Nature
and partial synthesis of the chick antidermatitic fac-
tor. J Am Chem Soc. 1939;61:977–978.
3. Jukes T.H. The pantothenic acid requirements of
the chick. J Biol Chem. 1939;129:225–231.
4. Spies TD, Stanberry SR, Williams RJ, Jukes TH,
Babcock SH. Pantothenic acid in human nutrition.
JAMA. 1940;115:523–524.
5. Williams RJ, Majors RT. The structure of pantoth-
enic acid. Science. 1040;91:246–248.
6. Plesofsky-Vig N, Brambi R. Pantothenic acid and
coenzyme A in cellular modification of proteins.
Annu Rev Nutr. 1988;8:461–482.
7. Wakil SJ. Fatty acid synthetase, a proficient multi-
functional enzyme. Biochemistry. 1989;28:4523–
4530.
8. Bird OD, Thompson RQ. Pantothenic acid. In:
Gyorgy P, Pearson WN, eds. The Vitamins.2nd ed.
New York: Academic Press; 1967; 209–241.
9. Shibata K, Gross CJ, Henderson LM. Hydrolysis
and absorption of pantothenate and its coenzymes
in the rat small intestine. J Nutr. 1983;113:
2207–2215.
10. Fenstermacher DK, Rose RC. Absorption of pan-
tothenic acid in rat and chick intestine. Am J Phys-
iol. 1986;250:G155–G160.
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
11. Said HM. Cellular uptake of biotin: mechanisms
and regulation. J Nutr. 1999;129:490S–493S.
12. Spector R, Mock DM. Biotin transport through the
blood-brain barrier. J Neurochem. 1987;48:400–
404.
13. Beinlich CJ, Naumovitz RD, Song WO, Neely JR.
Myocardial metabolism of pantothenic acid in
chronically diabetic rats. J Mol Cell Cardiol. 1990;
22:323–332.
14. Grassl SM. Human placental brush-border mem-
brane Na
-pantothenate cotransport. J Biol Chem.
1992;267:22902–22906.
15. Fisher MN, Robishaw JD, Neely JR. The properties
of and regulation of pantothenate kinase from rat
heart. J Biol Chem. 1985;256:15745–15751.
16. Rock CO, Calder RB, Karim MA, Jackowski S.
Pantothenate kinase regulation of the intracellular
concentration of coenzyme A. J Biol Chem. 2000;
275:1377–1383.
17. Kirschbaum N, Climons R, Marino KA, Sheedy G,
Nguygen M, Smith C. Pantothenate kinase activity
in livers of genetically diabetic mice (db/db) and
hormonally treated cultured rat hepatocytes. J Nutr.
1990;120:1376–1386.
18. Robishaw JD, Berkich D, Neely JR. Rate-limiting
step and control of coenzyme A synthesis in cardiac
muscle. J Biol Chem. 1982;257:10967–10972.
19. Reibel DK, Wyse BW, Berkich DA, Neely JR.
Regulation of coenzyme A synthesis in heart mus-
cle: effects of diabetes and fasting. Am J Physiol.
1981;240:H606–H611.
20. Bucovaz ET, MacLeod RM, Morrison JC, Why-
brew WD. The coenzyme A-synthesizing protein
complex and its proposed role in CoA biosynthesis
in bakers’ yeast. Biochimie. 1998;79:787–798.
21. Praphanphoj V, Sacksteder KA, Gould SJ, Thomas
GH, Geraghty MT. Identification of the alpha-
aminoadipic semialdehyde dehydrogenase phos-
phopantetheinyl transferase gene, the human or-
tholog of the yeast LYS5 gene. Mol Genet Metab.
2001;72:336–342.
22. Seo DW, Kim YK, Cho EJ, Han JW, Lee HY,
Hong S, Lee HW. Oligosaccharide-linked acyl car-
rier protein, a novel transmethylase inhibitor from
porcine liver inhibits cell growth. Arch Pharmacol
Res. 2002;25:463–468.
23. Raychaudhuri S, Rajasekharan R. Nonorganellar
acyl carrier protein from oleaginous yeast is a homo-
logue of ribosomal protein P2. J Biol Chem. 2003;
278:37648–37657.
24. Khosla C, Tang Y. Chemistry: a new route to de-
signer antibiotics. Science. 2005;308:367–368.
25. Nicholis DG, Ferguson SJ. Bioenergetics-3.Boston:
Academic Press; 2002; 1–207.
26. Smith CM, Milner RE. The mechanism of panto-
thenate transport by rat liver parenchymal cells in
Pantothenic Acid Miller, Rogers and Rucker 11
primary culture. J Biol Chem. 1985;260:4823–
4931.
27. Lopaschukf GD, Michalak M, Tsang H. Regula-
tion of pantothenic acid transport in the heart: in-
volvement of a Na
-cotransport system. J Biol
Chem. 1987;262:3615–3619.
28. Beinlich CJ, Robishaw JD, Neely JR. Metabolism
of pantothenic acid in hearts of diabetic rats. J
Molec Cell Cardiol. 1989;21:641–650.
29. Said HM, Ortiz A, McCloud E, Dyer D, Moyer
MP, Rubin S. Biotin uptake by human colonic epi-
thelial NCM460 cells: a carrier-mediated process
shared with pantothenic acid. Am J Physiol. 1998;
275:C1365–C1371.
30. Spector R. Development and characterization of
pantothenic acid transport in brain. J Neurochem.
1987;47:563–568.
31. Spector R. Pantothenic acid transport and metabo-
lism in the central nervous system. Am J Physiol.
1986;250:R292–R297.
32. Walsh JH, Wyse BW, Hansen RG. Pantothenic
acid content of 75 processed and cooked foods. J
Am Diet Assoc. 1981;78:140–144.
33. Robinson FA. The Vitamin Co-Factors of Enzyme
Systems.Oxford: Pergamon Press; 1966.
34. Schroeder HA. Losses of vitamins and trace min-
erals resulting from processing and preservation of
foods. Am J Clin Nutr. 1971;24:562–573.
35. Stein ED, Diamond JM. Do dietary levels of pan-
tothenic acid regulate its intestinal uptake in mice?
JNutr. 1989;119:1973–1983.
36. Food and Nutrition Board, Institute of Medicine.
Dietary Reference Intakes for Thiamin, Riboflavin,
Niacin, Vitamin B6, Folate, Vitamin B12, Pantoth-
enic Acid, Biotin, and Choline. Washington, DC:
National Academies Press; 1998. Available online
at: http://www.nap.edu/openbook/0309065542/
html/.
37. Tarr JB, Tamura T, Stokstad EL. Availability of
vitamin B6 and pantothenate in an average Ameri-
can diet in man. Am J Clin Nutr. 1981;34:
1328–1337.
38. Bull NL, Buss DH. Biotin, pantothenic acid and
vitamin E in the British household food supply.
Hum Nutr Appl Nutr. 1982;36:190–196.
39. Kathman JV, Kies C. Pantothenic acid status of
free-living adolescent and young adults. Nutr Res.
1984;4:245–250.
40. Srinivasan V, Christensen N, Wyse BW, Hansen
RG. Pantothenic acid nutritional status in the
elderly — institutionalized and non-institutional-
ized. Am J Clin Nutr. 1981;34:1736–1742.
41. Song WO, Wyse BW, Hansen RG. Pantothenic
acid status of pregnant and lactating women. J Am
Diet Assoc. 1985;85:192–198.
42. Deodhar AD, Ramakrishnan CV. Studies on
human lactation: relation between the dietary intake
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
of lactating women and the chemical composition of
milk with regard to vitamin content. J Trop Pediatr.
1961;6:44–70.
43. Cohenour SH, Calloway DH. Blood, urine, and
dietary pantothenic acid levels of pregnant teenag-
ers. Am J Clin Nutr. 1972;25:512–517.
44. Song WO, Chan GM, Wyse BW, Hansen RG.
Effect of PA status on the content of the vitamin
in human milk. Am J Clin Nutr. 1984;40:317–324.
45. Kerrey E, Crispin S, Fox HM, Kies C. Nutritional
status of preschool children. I. dietary and biochem-
ical findings. Am J Clin Nutr. 1968;21:1274–1279.
46. Pace JK, Stier LB, Taylor DD, Goodman PS. Met-
abolic patterns in preadolescent children. 5. intake
and urinary excretion of pantothenic acid and folic
acid. J Nutr. 1961;74:345–351.
47. Eissenstat BR, Wyse BW, Hansen RG. Pantoth-
enic acid status of adolescents. Am J Clin Nutr.
1986;44:931–937.
48. Wittwer CT, Schweitzer C, Pearson J, Song WO,
Windham CT, Wyse BW, Hansen RG. Enzymes
for liberation of pantothenic acid in blood: use of
plasma pantetheinase. Am J Clin Nutr. 1989;50:
1072–1078.
49. Kratzer FH, Williams DE. The pantothenic acid
requirement for poults for early growth. Poult Sci.
1948;27:518–523.
50. Milligan JL, Briggs GM. Replacement of pantoth-
enic acid by panthenol in chick diets. Poult Sci.
1949;28:202–205.
51. Gries CL, Scott ML. The pathology of thiamin,
riboflavin, pantothenic acid and niacin deficiencies
in the chick. J Nutr. 1972;102:1269–1285.
52. SubbaRow Y, Hitchings GH. Pantothenic acid as
afactor in rat nutrition. J Am Chem Soc. 1939;61:
1615–1618.
53. Sullivan M, Nicholls J. Nutritional dermatoses in
the rat: VI. the effect of pantothenic acid deficiency.
AMA Archives of Dermatology and Syphilology.
1942;45:917–932.
54. Eida K, Kubato N, Nishigaki T, et al. Harderian
gland: V. effect of dietary pantothenic acid defi-
ciency on porphyrin biosynthesis in Harderian
gland of rats. Chem Pharm Bull (Tokyo). 1975;23:
1–4.
55. Axelrod AE. Immune processes in vitamin defi-
ciency states. Am J Clin Nutr. 1971;24:265–271.
56. Pietrzik K, Hesse CH, Zur Wiesch ES, Hotzel D.
Urinary excretion of pantothenic acid as a measure-
ment of nutritional requirements. Int J Vit Nutr
Res. 1975;45:153–162.
57. Schaefer AE, McKibbin JM, Elvehjem CA. Pan-
tothenic acid deficiency in dogs. J Biol Chem. 1942;
143:321–330.
58. Noda S, Haratake J, Sasaki A, Ishii N, Umezaki
H, Horie A. Acute encephalopathy with hepatic
steatosis induced by pantothenic acid antagonist,
12 Present Knowledge in Nutrition, Ninth Edition Section V: Water-Soluble Vitamins and Related Nutrients
calcium hopantenate, in dogs. Liver. 1991;11:
134–142.
59. Wintrobe MM, Follis RH, Alcayaga R, Paulson M,
Humphreys S. Pantothenic acid deficiency in swine
with particular reference to the effects on growth
and on the alimentary tract. Bulletin of Johns Hop-
kins Hospital. 1943;73:313–319.
60. Nelson RA. Intestinal transport, coenzyme A, and
colitis in pantothenic acid deficiency. Am J Clin
Nutr. 1968;21:495–501.
61. Glusman M. The syndrome of “burning feet” (nu-
tritional melagia) as a manifestation of nutritional
deficiency. Am J Med. 1947;3:211–223.
62. Hodges RE, Ohlson MA, Bean WB. Pantothenic
acid deficiency in man. J Clin Invest. 1958;37:
1642–1657.
63. Hodges RE, Bean WB, Ohlson MA, Bleiler R.
Human pantothenic acid deficiency produced by
omega-methyl pantothenic acid. J Clin Invest.
1959;38:1421–1425.
64. Fry PC, Fox HM, Tao HG. Metabolic response to
apantothenic acid deficient diet in humans. J Nutr
Sci Vitaminol (Tokyo). 1976;22:339–346.
65. Fox HM, Linkswiler H. Pantothenic acid excretion
on three levels intake. J Nutr. 1961;75:451–454.
66. Annous KF, Song WO. Pantothenic acid uptake
and metabolism by red blood cells of rats. J Nutr.
1985;125:2586–2593.
67. Drell W, Dunn MS. Production of pantothenic acid
deficiency syndrome in mice with methylpantoth-
enic acid. Arch Biochem. 1951;33:110–119.
68. Noda S, Haratake J, Sasaki A, Ishii N, Umezaki
H, Horie A. Acute encephalopathy with hepatic
steatosis induced by pantothenic acid antagonist,
calcium hopantenate, in dogs. Liver. 1991;11:
134–142.
69. Noda S, Umezaki H, Yamamoto K, Araki T, Mura-
kami T, Ishii N. Reye’s-like syndrome following
treatment with the pantothenic acid antagonist, cal-
cium hopantenate. J Neurol Neurosurg Psychiatr.
1998;51:582–585.
70. Ralli EP, Dumm ME. Relation of pantothenic acid
to adrenal cortical function. Vitam Horm. 1953;11:
133–158.
71. Tahiliani AG, Beinlich CJ. Pantothenic acid in
health and disease. Vitam Horm. 1991;46:
165–228.
72. Sauberlich HE. Pantothenic acid. In: Laboratory
Tests for the Assessment of Nutritional Status.2nd ed.
Boca Raton, FL: CRC Press; 1999; 175–183.
73. Avogaro P, Bittolo Bon G, Fusello M. Effects of
pantethine on lipids, lipoproteins and apolipoprot-
eins in man. Current Therapeutic Research. 1983;
33:488–493.
74. Gaddi A, Descovich GC, Noseda G, et al. Con-
trolled evaluation of pantethine, a natural hypolip-
idemic compound, in patients with different forms
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
of hyperlipoproteinemia. Atherosclerosis. 1984;50:
73–83.
75. Bertolini S, Donati C, Elicio N, et al. Lipoprotein
changes induced by pantethine in hyperlipopro-
teinemic patients: adults and children. Int J Clin
Pharmacol Ther Toxicol. 1986;24:630–637.
76. Arsenio L, Bodria P, Magnati G, Starta A, Trovato
R. Effectiveness of long-term treatment with pan-
tethine in patients with dyslipidemia. Clin Ther.
1986;8:537–545.
77. Miccoli R, Marchetti P, Sampietro T, Benzi L,
Tognarelli M, Navalesi R. Effects of pantethine on
lipids and apolipoproteins in hypercholesterolemic
diabetic and nondiabetic patients. Current Thera-
peutic Research. 1984;36:545–549.
78. Binaghi P, Cellina G, Lo Cicero G, Bruschi F,
Porcaro E, Penotti M. Evaluation of the choles-
terol-lowering effectiveness of pantethine in women
in perimenopausal age. Minerva Medica. 1990;81:
475–479.
79. Kameda K, Abiko Y. Stimulation of fatty acid me-
tabolism by pantethine. In: Cavallini D, Gaull GE,
Zappia V, eds. Natural Sulfur Compounds.New
York: Plenum Press; 1980; 443–452.
80. Cighetti G, Del Puppo M, Paroni R, Galli G,
Kienle MG. Modulation of HMG-CoA reductase
activity by pantetheine/pantethine. Biochim Bio-
phys Acta. 1988;963:389–393.
81. Cighetti G, Del Puppo M, Paroni R, Fiorica E,
Galli G, Kienle MG. Pantethine inhibits choles-
terol and fatty acid syntheses and stimulates carbon
dioxide formation in isolated rat hepatocytes. J Lip
Res. 1987;28:152–161.
82. Cighetti G, Del Puppo M, Paroni R, Galli G,
Kienle MG. Effects of pantethine on cholesterol
synthesis from mevalonate in isolated rat hepato-
cytes. Atherosclerosis. 1986;60:67–77.
83. Shock NW, Sebrell WH. The effect of changes in
concentration of pantothenate on the work output
of perfused frog muscles. Am J Physiol. 1944;142:
274–278.
84. Ralli EP. Effects of dietary supplementation on the
ability of rats to withstand exposure to cold. Nutr
Rev. 1968;26:124.
85. Smith CM, Narrow CM, Kendrick ZV, Steffen C.
The effect of pantothenate deficiency in mice on
their metabolic response to fast and exercise. Me-
tabolism. 1987;36:115–121.
86. Litoff D, Scherzer H, Harrison J. Effects of pan-
tothenic acid supplementation on human exercise.
Med Sci Sports Exerc. 1985;17(suppl):287.
87. Nice C, Reeves A, Brinck-Johnson T, Noll W. The
effects of pantothenic acid on human exercise ca-
pacity. J Sports Med Phys Fitness. 1984;24:26–29.
88. Webster MJ. Physiological and performance re-
sponses to supplementation with thiamin and pan-
Pantothenic Acid Miller, Rogers and Rucker 13
tothenic acid derivatives. Eur J Appl Physiol. 1998;
77:486–491.
89. Nelson MM, Sulon E, Becks H, Wainwright WW,
Evans HM. Changes in endochondral ossification
of the tibia accompanying acute pantothenic acid
deficiency in young rats. Proceedings of the Society
of Experimental Biology and Medicine. 1950;73:
31–36.
90. Barton-Wright EC, Elliot WA. The pantothenic
acid metabolism of rheumatoid arthritis. Lancet.
1963;2:862–863.
91. U.S. General Practitioner Research Group. Cal-
cium pantothenate in arthritic conditions. a report
from the general practitioner research group. Practi-
tioner. 1980;224:208–211.
92. Weimann BI, Hermann D. Studies on wound heal-
ing: effects of calcium D-pantothenate on the mi-
gration, proliferation and protein synthesis of
human dermal fibroblasts in culture. Int J Vitam
Nutr Res. 1999;69:113–119.
93. Vaxman F, Olender S, Lambert A, et al. Effect of
pantothenic acid and ascorbic acid supplementation
on human skin wound healing process. A double-
blind, prospective and randomized trial. Eur Surg
Res. 1995;27:158–166.
94. Vaxman F, Olender S, Lambert A, et al. Can the
wound healing process be improved by vitamin sup-
plementation? Experimental study on humans. Eur
Surg Res. 1996;28:306–314.
95. Schmuth M, Wimmer MA, Hofer S, et al. Topical
AG-PPKN-0909 R1 CH25 04-04-06 07:27:58
corticosteroid therapy for acute radiation dermatitis:
aprospective, randomized, double-blind study. Br
JDermatol. 2002;146:983–991.
96. Biro K, Thaci D, Ochsendorf FR, et al. Efficacy of
dexpanthenol in skin protection against irritation:
adouble-blind, placebo-controlled study. Contact
Dermatitis. 2003;49:80–84.
97. Romiti R, Romiti N. Dexpanthenol cream signifi-
cantly improves mucocutaneous side effects associ-
ated with isotretinoin therapy. Pediatr Dermatol.
2002;19:368–371.
98. Leung LH. Systemic lupus erythematosus: a com-
bined deficiency disease. Med Hypotheses. 2004;
62:922–924.
99. Goldman L. Intensive panthenol therapy of lupus
erythematosus. J Invest Dermatol. 1950;15:291–
293.
100. Welsh, AL. Lupus erythematosus: treatment by
combined use of massive amounts of calcium panto-
thenate or panthenol with synthetic vitamin E.
AMA Archives of Dermatology and Syphilology.
1952;65:137–148.
101. Welsh AL. Lupus erythematosus: treatment by
combined use of massive amounts of pantothenic
acid and vitamin E. AMA Archives of Dermatology
and Syphilology. 1954;70:181–198.
102. Chochrane T, Leslie G. The treatment of lupus
erythematosus with calcium pantothenate and pan-
thenol. J Invest Dermatol. 1952;18:365–367.
... Pantothenic acid is a precursor of two coenzymes, coenzyme A (CoA) and acyl-carrier-protein. The coenzymes of this vitamin participate in various metabolic reactions, such as glucose, fatty acids and amino acids entering into energy-yielding tricarboxylic acid (TCA) cycle, fatty acid oxidation and synthesis, cholesterol synthesis, acetylcholine synthesis, and heme synthesis etc. [1,2]. Its importance is highlighted by the adverse effects of pantothenic acid deficiency (PAD) in mammals such as rats, cats, and pigs, including growth depression, skin lesions, diarrhea, loss of hair [2][3][4][5][6]. ...
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Background Pantothenic acid deficiency (PAD) results in growth depression and intestinal hypofunction of animals. However, the underlying molecular mechanisms remain to be elucidated. Mucosal proteome might reflect dietary influences on physiological processes. Results A total of 128 white Pekin ducks of one-day-old were randomly assigned to two groups, fed either a PAD or a pantothenic acid adequate (control, CON) diet. After a 16-day feeding period, two ducks from each replicate were sampled to measure plasma parameters, intestinal morphology, and mucosal proteome. Compared to the CON group, high mortality, growth retardation, fasting hypoglycemia, reduced plasma insulin, and oxidative stress were observed in the PAD group. Furthermore, PAD induced morphological alterations of the small intestine indicated by reduced villus height and villus surface area of duodenum, jejunum, and ileum. The duodenum mucosal proteome of ducks showed that 198 proteins were up-regulated and 223 proteins were down-regulated (> 1.5-fold change) in the PAD group compared to those in the CON group. Selected proteins were confirmed by Western blotting. Pathway analysis of these proteins exhibited the suppression of glycolysis and gluconeogenesis, fatty acid beta oxidation, tricarboxylic acid cycle, oxidative phosphorylation, oxidative stress, and intestinal absorption in the PAD group, indicating impaired energy generation and abnormal intestinal absorption. We also show that nine out of eleven proteins involved in regulation of actin cytoskeleton were up-regulated by PAD, probably indicates reduced intestinal integrity. Conclusion PAD leads to growth depression and intestinal hypofunction of ducks, which are associated with impaired energy generation, abnormal intestinal absorption, and regulation of actin cytoskeleton processes. These findings provide insights into the mechanisms of intestinal hypofunction induced by PAD.
... Pantothenic acid is available in a variety of foods, usually as a component of coenzyme A (CoA) and 4'-phosphopantetheine. Upon ingestion, dietary coenzyme A and phosphopantetheine are hydrolyzed to pantothenic acid prior to intestinal absorption (Miller and Rucker 2012). Animal liver and kidney, fish, shellfish, pork, chicken, egg yolk, milk, yogurt, legumes, mushrooms, avocados, broccoli, breadfruit, and sweet potatoes are good sources of pantothenic acid. ...
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A plant-based diet (PBD) can provide numerous health benefits for patients with cardiovascular risk factors. However, an inadequately planned PBD also bear the potential for deficiencies in certain macro- and micronutrients. The present study analyzed nutrient profiles of individuals who adopted a PBD as part of the CardioVeg study. Participants with cardiovascular risk factors were randomly assigned to either a whole-food PBD intervention (n = 36; eight 90 min group meetings including two 120 min cooking sessions) or a control group asked to maintain an omnivorous diet (n = 34) for eight weeks. Food intake data were collected using three-day weighed food records and analyzed with NutriGuide software, including the German Nutrient Data Base (German: Bundeslebensmittelschlüssel). Nutrient intake was compared before and after eight weeks as well as between the groups. The results for both groups were then contrasted to the current dietary recommendations published by the societies for nutrition in Germany, Austria, and Switzerland. Moreover, anthropometric/laboratory data and ambulatory blood pressure monitoring were determined at baseline and after 8 weeks. Data of a subsample (n = 18 in the PBD group and n = 19 in the control group) were used for the present analyses of the dietary intake data. A PBD yielded several benefits including (but not limited to) a lower energy density, a lower intake of cholesterol and saturated fat, an increased consumption of fiber, and a lower intake of salt. Recommended intakes of most vitamins and minerals were generally met, except for vitamin B12 in the PBD group. A low intake of several other critical nutrients (vitamin D, iodine) was observed in both groups. Compared with the control group, PBD resulted in a significant decrease in body weight, body mass index, waist circumference, HbA1c, and fasting blood glucose after 8 weeks. Overall, it can be concluded that a PBD had a more favorable nutrient composition for cardiovascular health than the omnivorous dietary pattern of the control group.
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Background and aims: Vitamins are bioactive compounds naturally found in many different types of food and required by the human body for many biological functions and enzymatic activities. Due to their antioxidant properties, certain vitamin derivatives have been synthesized for inclusion in many cosmetics, thus leading to an increasing incidence of allergic contact dermatitis (ACD) cases. Therefore, the present review may be helpful to provide an insight into the sensitizing role of at least certain vitamins and may also offer possible patch test alternatives for definitive diagnosis. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Literature search regarding ACD cases to vitamins was performed using the Medline, PubMed, Scopus, EMBASE, and Google Scholar databases from January 1940 up to June 2021. Results: A total of 4494 articles matched the keywords used for the researched. Records removed before screening included 15 duplicate articles and 3429 not eligible articles (e.g., not written in English, studies on animals, not relevant to the topic). A total of 1050 articles underwent the screening phase and 258 were therefore excluded as they were not primary studies. Subsequentially, 792 articles were considered eligible for the review and 688 of them were finally excluded as they did not report the outcome of interest. Therefore, 104 articles were definitely included in the present review. Conclusion: ACD to vitamins is still probably an underestimated issue in cosmetology, as many vitamins are considered "natural" and therefore "safe" ingredients. On the contrary, according to current literature, almost all vitamins contained in topical products are able to induce allergic reactions, with the exception of vitamin B2 and vitamin B9. Patch tests are not standardized, thus leading to difficulties in diagnosis.
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Pantothenic acid deficiency (PAD) in animals causes growth depression, fasting hypoglycemia and impaired lipid and glucose metabolism. However, a systematic multi-omics analysis of effects of PAD on hepatic function has apparently not been reported. We investigated liver proteome and metabolome changes induced by PAD to explain its effects on growth and liver metabolic disorders. Pekin ducks (1-d-old, n=128) were allocated into 2 groups, with 8 replicates and 8 birds per replicate. For 16 d, all ducks had ad libitum access to either a PAD or a pantothenic acid adequate (control, CON) diet, formulated by supplementing a basal diet with 0 or 8 mg pantothenic acid/kg of diet, respectively. Liver enlargement, elevated liver glycogen concentrations and decreased liver concentrations of triglyceride and unsaturated fatty acids were present in the PAD group compared to the CON group. Based on integrated liver proteomics and metabolomics, PAD mainly affected glycogen synthesis and degradation, glycolysis and gluconeogenesis, tricarboxylic acid (TCA) cycle, peroxisome proliferator-activated receptor (PPAR) signaling pathway, fatty acid beta oxidation, and oxidative phosphorylation. Selected proteins were confirmed by Western blotting. Downregulation of proteins and metabolites involved in glycogen synthesis and degradation, glycolysis and gluconeogenesis implied that these processes were impaired in PAD ducks, which could have contributed to fasting hypoglycemia, liver glycogen storage, insufficient ATP production, and growth retardation. In contrast, PAD also upregulated proteins and metabolites involved in fatty acid beta oxidation, the TCA cycle, and oxidative phosphorylation processes in the liver; presumably compensatory responses to produce ATP. We inferred that PAD decreased liver triglyceride and unsaturated fatty acids by activating fatty acid beta oxidation and impairing unsaturated fatty acid synthesis. These findings contributed to our understanding of the mechanisms of PAD-induced changes in hepatic metabolism.
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This review summarizes the current knowledge on essential vitamins B1, B2, B3, and B5. These B-complex vitamins must be taken from diet, with the exception of vitamin B3, that can also be synthetized from amino acid tryptophan. All of these vitamins are water soluble, which determines their main properties, namely: they are partly lost when food is washed or boiled since they migrate to the water; the requirement of membrane transporters for their permeation into the cells; and their safety since any excess is rapidly eliminated via the kidney. The therapeutic use of B-complex vitamins is mostly limited to hypovitaminoses or similar conditions, but, as they are generally very safe, they have also been examined in other pathological conditions. Nicotinic acid, a form of vitamin B3, is the only exception because it is a known hypolipidemic agent in gram doses. The article also sums up: (i) the current methods for detection of the vitamins of the B-complex in biological fluids; (ii) the food and other sources of these vitamins including the effect of common processing and storage methods on their content; and (iii) their physiological function.
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Vitamin B5 (d-pantothenic acid; pantothenate) is an essential trace nutrient that functions as the obligate precursor of coenzyme A (CoA), through which it plays key roles in myriad biological processes, including many that regulate carbohydrate, lipid, protein, and nucleic acid metabolism. In the brain, acetyl-CoA is necessary for synthesis of the complex fatty-acyl chains of myelin, and of the neurotransmitter acetylcholine. We recently found that cerebral pantothenate is markedly lowered, averaging ∼55% of control values in cases of Huntington's disease (HD) including those who are pre-symptomatic, and that regions where pantothenate is lowered correspond to those which are more severely damaged. Here we sought to determine the previously unknown distribution of pantothenate in the normal-rat brain, and whether the diabetic rat might be useful as a model for altered cerebral pantothenate metabolism. We employed histological staining (Nissl) to identify brain structures; immunohistochemistry with anti-pantothenate antibodies to determine the distribution of pantothenate in caudate putamen and cerebellum; and gas-chromatography/mass-spectrometry to quantitate levels of pantothenate and other metabolites in normal- and diabetic-rat brain. Remarkably, cerebral pantothenate was almost entirely localized to myelin-containing structures in both experimental groups. Diabetes did not modify levels or disposition of cerebral pantothenate. These findings are consistent with physiological localization of pantothenate in myelinated white-matter structures, where it could serve to support myelin synthesis. Further investigation of cerebral pantothenate is warranted in neurodegenerative diseases such as HD and Alzheimer's disease, where myelin loss is a known characteristic of pathogenesis.
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The availability of vitamin B6 and pantothenate in an average American diet was assessed in healthy male volunteers. The subjects received two types of diets, both nutritionally equivalent to the average American diet: period 1 (35 days), semipurified formula diet (low in both vitamins) with daily supplements of 1.1 mg pyridoxine and 8.2 mg pantothenate; period 2 (35 days), natural food sources, providing 2.3 mg vitamin B6 and 11.5 mg pantothenate/day; period 3 (21 days), formula diet, providing 2.7 mg pyridoxine and 8.2 mg pantothenate/day. Daily protein intake was 96 g throughout the study. Vitamins in food and urine samples were determined microbiologically and plasma pyridoxal phosphate by a tyrosine apodecarboxylase radioassay method. Compared to the availability of the pure vitamins as 100%, the availability of vitamin B6 ranged from 61 to 81% with a mean of 71% using plasma pyridoxal phosphate data, and ranged from 73 to 92% with a mean of 79% according to urinary vitamin B6 data. Availability of pantothenate ranged from 40 to 61% with a mean of 50%, according to urinary pantothenate data. The average American diet used in our study contained 1.7 and 5.8 mg/day of available vitamin B6 and pantothenate, respectively.
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Seventeen lactating women who delivered preterm infants (between 28 to 34 wk of gestational age) and 26 nursing mothers of term infants participated in the study. Each term mother kept a record of 2-day dietary intakes, collected urines for 2 days, and provided fore and hind milk samples and a fasting blood sample at 2 and 12 wk postpartum. Each of preterm women provided fore and hind milk samples once a week for 16 wk starting 2 wk postpartum. The method of determining pantothenic acid content in milk samples was validated, and the vitamin was quantitated by the radioimmunoassay. The average pantothenate levels in fore and hind samples of preterm milk (3.31 and 3.72 µg/ml, respectively) were significantly (p < 0.05) higher than those of term milk (2.64 and 2.48 µg/ml, respectively). No significant change was observed in pantothenic acid content within a feeding or with the progress of nursing in both groups. The vitamin content of human milk was compared with the minimum requirement of the Infant Formula Act of 1980. The panthothenate level in term milk was significantly (p < 0.05) correlated with the vitamin level in maternal circulation and with that of the dietary intake and urinary excretion.
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Pantothenic acid and folic acid content of food and urine was determined for 35 girls, 7 to 9 years of age, maintained with controlled diets. Three series of metabolic studies were made. Pantothenic acid intakes in the three studies averaged 4.49, 5.00, and 2.79 mg per child per day; urinary excretions averaged 2.85, 1.71, and 1.31 mg per day, respectively. In general, with the higher intakes of pantothenic acid the urinary excretion tended to be higher. With an increased protein intake there was an increased pantothenic acid intake since many of the foods high in pantothenic acid are likely to contain considerable protein. Pantothenic acid excretion for the girls in these studies could not be related to body size. Folic acid intake in the three studies averaged 98, 80, and 52 µg per child per day; urinary excretion averaged 1.24, 1.13, and 1.41 µg per day, respectively. Excretion of folic acid in the urine accounted for less than 3% of the intake. The amount excreted did not show relationship to folic acid intake, pantothenic acid intake, protein intake, or body weight. Diets, made up of ordinary foods planned to meet the National Research Council's recommended allowances of well known nutrients for children 7 to 9 years of age, supplied from 4 to 5 mg of pantothenic acid and from 80 to 100 µg of folic acid per day.
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In the chronic therapy of hyperlipidaemia active drugs with low side effects should be used. In this paper we report the results obtained employing pantethine in the treatment of 20 hypercholesterolemic diabetic and non-diabetic patients. After three months of therapy, total cholesterol and LDL-cholesterol decreased significantly both in non-diabetics (p<0.05) and in diabetics (p<0.01). No significant variations were observed for the other lipid parameters and apolipoproteins A and B. Thus the effectiveness of pantethine is demonstrated in reducing total and LDL cholesterol both in diabetic and non-diabetic moderately hypercholesterolemic patients with the absence of any important side effects.
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Diabetes mellitus is a metabolic disease where lack of insulin action diminishes glucose utilization in the peripheral tissues. In compensation for this abnormal situation, fat is preferentially used as a sole energy source in the body. The metabolic shift to lipid utilization leads to hypertriglyceridemia accompanied by elevation of free fattyacid in blood and, in very advanced stages by elevation of ketone bodies including acetoacetate and ß-hydroxybutyrate in blood. Increased level of CoA and acyl CoA in the diabetic rat liver was reported by Smith et al. [1]. This seems to be a metabolic response to increased utilization of fatty acid in diabetic state and suggests increased requirement for CoA in diabetic tissues. It is, therefore, interesting to study the effect of some precursors of CoA on diabetic hyperlipidemia. The present paper deals with a favorable effect of pantethine on lipid metabolism in streptozotocin diabetic rats. Pantethine treatment has been found to reduce increased levels of serum triglycerides, free fatty acid and ß-hydroxybutyrate in diabetic rats, but pantothenic acid had no effect. For getting insight into the mode of the specific action of pantethine, have been carried out some experiment in vitro including fatty acid oxidation and ketogenesis in rat liver and muscle tissues.
Article
The present study confirmed that pantethine significantly reduced cholesterol (total and LDL) and triglyceride and increased HDL cholesterol and apoprotein A-I. An appreciable effect was also seen on apoprotein B (LDL) whose atherogenic value has been recently reported. On the whole this purely preliminary study was satisfactory in that it showed that this natural substance, an important component of CoA, is definitely effective in reducing blood lipids, through a complex action involving lipids, lipoproteins, and apolipoproteins. Other studies are needed to clarify whether the drug is also useful in the treament of major hyperlipidaemia and, above all, in genetic conditions.