Post on 30-Mar-2016
description
Vitami
L-glutathione
vitamin B1
vitamin B
vitamin B12 vitamin C
vitamin B1 vitamin D vitamin E
folic acid
L-glutathione
chromium picolinate
coenzyme Q10
DHEA
Melatonin bioflavonoids
Rutin Acetylsaliclyic acid
α-lipoic acid
β-carotene
potassium
selenium zinc
magnesium
garlic
ginger
Gingko biloba cod liver oil flaxseed oil ginseng reen tea extract
coenzyme Q10
Gingko biloba
Melatonin
vitamin B1
vitamin B6
vitamin B12 vitamin C
vitamin B1 vitamin D vitamin E
folic acid
L-glutathione
chromium picolinate
Coenzyme
DHEA
Melatonin
bioflavono
Rutin Acetylsaliclyic acid
α-lipoic acid
β-carotene
potassium selenium zinc
magnesium
garlic
ginger
cod liver oil
flaxseed oil
green tea extract
coenzyme Q10 bioflavonoids
Melatonin
vitamin B1
vitamin B6 vitamin B3
vitamin B12 vitamin C
vitamin B1 vitamin D vitamin E
folic acid
n-acetyl cysteine L-glutathione
chromium picolinate
coenzyme Q10
DHEA
Melatonin
bioflavonoids
Rutin Acetylsaliclyic acid
α-lipoic acid
β-carotene
potassium
selenium zinc
magnesium
garlic
ginger
Gingko biloba cod liver oil flaxseed oil ginseng reen tea extract
coenzyme Q10
Gingko biloba
bioflavonoids
Melatonin
vitamin B1
vitamin B12 Vita
vitamin D vitamin E
folic acid L-glutathione
coenzyme Q10
DHEA
Me
bioflavonoids
Rutin Acetylsaliclyic acid
ic acid β-ca
otassium magne
garlic ginger
Gingko biloba cod liver oil flaxseed oil ginseng
coenzyme Q10
Gingko biloba
bioflavonoids
Melatonin L-glutathione
Melatonin
Acetylsaliclyic acid
β
β
Acetylsaliclyic acid
β-carotene DHEA
ginseng Mela
Flaxseed
complex dietary supplement
DSP
a “cure” to aging?
Biochemistry 3D03 Metabolism “Your Way” Project
McMaster University © 2012
Authors: Shanthiya Baheerathan, Qian Feng, Vivian Shan, Austin Yan
Prepared for: Dr. Michelle MacDonald, TA: Rabia Mateen
Preface
Aging is the inevitable process of continuous growth and
change in an organism’s lifetime. Recently, research by Dr. Rollo et
al. at McMaster University suggested a possible “cure” to aging. A
dietary supplement (DSP) developed by him in 2003, composed of
thirty-one natural and synthetic compounds, showed anti-aging
effects in mice. This booklet presents a detailed review of the
individual ingredients in the DSP and the pathways through which
each ingredient is metabolized. By looking at how the metabolic
pathways of each ingredient interact with each other, and with
other chemicals and enzymes in the body, this booklet provides
insights into the mechanisms through which the dietary
supplement works to accomplish its anti-aging effects.
i
Table of Contents
Introduction 1
Compound profiles
Vitamin B1 ● ● ● ● ● ● 3
Vitamin B3 ● ● ● ● ● ● 5
Vitamin B6 ● ● ● ● ● ● 7
Vitamin B12 ● ● ● ● ● ● 9
Vitamin C ● ● ● ● ● ● 11
Vitamin D ● ● ● ● ● ● 13
Vitamin E ● ● ● ● ● ● 15
Folic acid ● ● ● ● ● ● 17
N-acetyl cysteine ● ● ● ● ● ● 19
L-glutathione ● ● ● ● ● ● 21
Acetyl L-carnitine ● ● ● ● ● ● 23
Chromium picolinate ● ● ● ● ● ● 25
Coenzyme Q10 ● ● ● ● ● ● 27
DHEA ● ● ● ● ● ● 29
Melatonin ● ● ● ● ● ● 31
Beta-carotene ● ● ● ● ● ● 33
Bioflavonoids ● ● ● ● ● ● 35
Rutin ● ● ● ● ● ● 37
Acetylsalicylic acid ● ● ● ● ● ● 39
Alpha-lipoic acid ● ● ● ● ● ● 41
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List of Compounds
Potassium ● ● ● ● ● ● 43
Selenium ● ● ● ● ● ● 44
Zinc ● ● ● ● ● ● 45
Magnesium ● ● ● ● ● ● 46
Garlic ● ● ● ● ● ● 47
Ginger ● ● ● ● ● ● 49
Gingko biloba ● ● ● ● ● ● 51
Cod liver oil ● ● ● ● ● ● 53
Flax seed oil ● ● ● ● ● ● 55
Ginseng ● ● ● ● ● ● 57
Green tea extract ● ● ● ● ● ● 59
How compounds interact 61
Interaction diagram 64
Conclusion 65
References 66
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Aging has been a very active area of research because many
age-related deterioration problems and pathologies affect
millions of patients worldwide. Neurological diseases such as
Alzheimer’s and Parkinson’s diseases have been associated with
age-related cognitive declines, while aging is also related to many
cancers [1]. These diseases are incurable and significantly affect
one’s quality of life. Thus, it is very important to understand the
process of aging in order to develop possible interventions to
alleviate some of its detrimental consequences.
It has been postulated that mitochondrial decay plays a
significant role in aging due to the accumulation of reactive
oxygen species as by-products of the electron transport chain [2].
This makes the mitochondria a victim of its own by-products. As
the damage accumulates, many different cellular processes are
disrupted, including detoxification, cell repair systems, DNA
replication, and osmotic balance. Higher processes like cognitive
function are also affected by the accumulation of oxidative
damage [3].
There are various dietary supplements sold over the counter
that claim to have anti-aging properties. Some of these
supplements, such as vitamins, N-acetyl cysteine and glutathione,
work as antioxidants to scavenge reactive oxygen species in order
to reduce mitochondrial damage [4, 5]. Instead of studying each
individual supplement, Dr. David Rollo et al. took a novel
approach in which they developed a complex dietary supplement
(DSP) made of 31 ingredients that are commonly available. A list
of these ingredients can be found on the Table of Contents on the
previous two pages.
Introduction
1
The DSP was designed to target five key mechanisms of
aging, including oxidative stress, inflammation, mitochondrial
function, insulin resistance, and membrane integrity. Using models
of transgenic growth-hormone mice that expressed accelerated
aging properties, Dr. Rollo et al. demonstrated in 2003, 2010 and
2011 that the complex DSP markedly improved learning, extended
longevity, prevented age-related motor function decline, and
increased cognitive ability [6, 7, 8].
Despite the benefits of the complex dietary supplement
shown in mice, there is currently no sufficient explanation on how
the cocktail of supplements work together to achieve its anti-
aging properties, especially in regards to the mechanisms on how
the compounds function and interact. To attempt to answer this
question, this booklet shows an investigation into the molecular
mechanisms of each of the 31 supplements listed in the DSP, and
draws many connections between the DSP’s individual
components.
Pages 3 to 60 of this booklet provide an information page for
each compound in the DSP, featuring a basic description of the
compound, its metabolic pathways and significance, and its
effects and functions in the body, especially in relation to anti-
aging properties. Each compound is also labelled with a
combination of tags that represent six categories of potential
anti-aging roles: anti-carcinogenic, antioxidant, anti-inflammatory,
anti-coagulant, neuroprotective, and insulin-sensitive. The dosage
provided at the top of each page refers to the daily dose that was
used in the studies by Dr. Rollo et al. for each mouse. Page 61 to
64 details potential compound metabolism connections and has
an interaction map on page 64 that summarizes the possible
interactions between each of the compounds. These links provide
insights into the mechanisms through which the DSP works to
achieve its anti-aging properties.
2
Vitamin B1
Description:
Thiamin is a water soluble B
vitamin. The vitamin is found in
the germ layers of cereal grains,
yeast, nuts and meat. Known to
play a critical role in energy
metabolism, B1 needs to be
replenished daily [1]. No
Tolerable Upper Intake level has
been derived for thiamin, but up
to 50 mg has been consumed
without any adverse effects [2].
3
Quick Facts:
Properties: Polar, amino acid
derivative
Molar Mass: 300.821 g/mol
Figure 1: thiamin
Metabolism:
Thiamin is found in humans as
thiamin phosphate derivatives:
monophosphate (ThMP), thiamin
triphosphate (ThTP)and thiamin
py rophospa te ( ThDP) , and
Adenosine thiamin Triphosphate
(AThTP) [3]. ThDP, the more well
known derivative, is a coenzyme
for many enzymes that catalyze
the transfer of two carbon units,
and for the dehydrogenation of
2-oxoacids. ThDP is required as a
coenzyme for pyruvate dehydro-
genase, alpha-ketoglutarate
dehydrogenase, and branched
chain keto acid dehydrogenase.
All of the above enzymes are
Dose: 0.72 mg/day | anti-carcinogenic | antioxidant | neuroprotective
required for carbohydrate metabolism
and neurotransmitter production.
ThDP is also a coenzyme for
Transketolase, which catalyzes critical
reactions, needed for the synthesis
energy ribonucleotides, nucleotides,
and NADPH [1,3].
ThTP is thought to be a neuroactive
form of thiamin, but recently, it has
been found that it can metabolize
certain proteins and was found to play
a role in cell signaling [4]. ThMP does
not have any known functions but was
found to be lower in Alzheimer’s
patients [3]. AThTP’s role is completely
unknown [3].
Effects: Beriberi and Wernicke Korsakoff syndrome result due to low ThDP
levels, causing decreased activity in enzymes. An increased intake of
thiamin will diminish the effects of both the diseases [3]. Increased thiamin
intake has been connected to a lower incidence of tumor proliferation [5],
and has a protective effect against Alzheimer’s disease [4]. Thiamin has
also been found to decrease depression [4]. Moreover, it acts as an
antioxidant [6] and a anti-carcinogenic agent [7].
References: [1] Conner R.; Straub G.; Ind. Eng. Chem Anal Ed 1941. 13 (6): 385-388.
[2] Dipalma JR.; Ritchie DM.; Ann. Rev. Pharmacol Toxicol 1966. 17:133-148 .
[3] Lonsdale D. ; Evid. Based Complement Alternat. Med. 2006. 3(1):49-59 .
[4] Ba A.; Cell Mol Neurobiol. 2008. 28(7)923-31.
[5] Bettendorff L.; Wins P.; The Febs Journal 2009. 276: 2917-2925.
[6] Basu TK.; Dickerson JWT.; Oncology. 1976. 33:250-252.
[7] Heseker H.; Kubler W.; Pudel V.; Westenhoffer J. Annals of New York Academy Of Sciences 1992. 669:
352-357. 4
Figure 2: Pathway for ThDP, ThMP, AThTp production [3].
Related Compounds: Folic acid (page 17), Green tea extract (page 59)
Vitamin B3
Description:
Niacin is a water soluble vitamin of
the B complex, and it said to be
involved in DNA repair, and the
production of several hormones
[1]. Too much niacin may lead to
dermatological conditions such as
skin flushing and itching, dry skin
and skin rashes. B3 can be found
in most animal products and some
fruits and vegetables, seeds and
fungi. Niacin can also be
synthesized from tryptophan by
the body [2]. This vitamin has been
found to be toxic at doses greater
than 3 g/day [3].
Quick Facts:
Properties: Water soluble
Molecular Mass: 123.1 g/mol
Figure 1: Pyridoxol Phosphate
Metabolism:
There exist different forms of
Vitamin B3, the two most
common: nicotinamide and
niacin. While the two derivatives
are very similar, nicotinamide
does not have the same lipid
modifying effects as niacin.
Both compounds are able to be
converted to NAD, and NADP in
vivo. Almost 200 enzymes use
niacin coenzymes: NAD and
NADP as acceptors and donators
of electrons in redox reactions.
Dose: 0.72 mg/day | anti-carcinogenic | antioxidant | neuroprotective
NAD is used in energy producing
reactions that involve the catabolism
of carbohydrates, fats, proteins and
alcohols. NADP is involved in anabolic
reactions, and the synthesis of
macromolecules such as fatty acids
and cholesterol.
NAD is also involved in non-redox
reactions, and NAD acts as a substrate
for two classes of enzymes that
separate niacin from NAD and transfer
ADP-ribose to proteins. This process
is hypothesized to act in cell signaling
by working on G-proteins [4].
5
6
Figure 2: The NAD molecule,
the molecule in red is vitamin B3.
Effects:
Early stages of niacin deficiency
slows down metabolism, while
severe deficiency leads to
pellegra [5].
Niacin also binds to and inhibits
the G-protein-coupled receptor
that helps with fat breakdown.
This fat that breaks off adipose
tissue is called very low density
lipoproteins make low density
lipoproteins. Niacin indirectly
influences the increase in HDL
concentrations of the blood. For
this reason, niacin has been
prescribed to those who are at risk for
heart disease [6]. Studies have even
shown that niacin is more effective
than Exetimibe, an anticoagulant [7].
Increased niacin intake has also shown
reduced inflammation and increased
flexibility in arthritis patients [8].
Finally, niacin has been found to be
anticarcinogenic (for oral and oesop-
hageal cancers) when in combination
with antioxidant [9].
References: [1] Shibata K; Toda S; Bioscience, Biotechnology, and Biochemistry 1997. 7: 1200-1202.
[2] Godsmith G.; American Journal of Clinical Nutrition 1958. 6:479-486.
[3] Knip M; Douek IF; Moore WP; Diabetologia. 2000. 43 (11): 1337–45.
[4] Jacobson E; Jacobson M; Methods in Enzymology. 1997 280-221-230
[5] Malfait P; Moren A; Dillon JC; Brodel A; Begkoyian G; Etchgorry MG; Malenga G; Hakewill P; Int. J.
Epidemiol. 1993. 22(3): 504-511.
[6] Ganji SH; Kamanna VS; Kashyap ML; The Journal of Nutritional Biochemistry. 2002. 14: 298-305.
[7] Allen JT; Villines TCl Stanek EJ; Devine PJ; Griffen L; N Engl J Med 2009. 361: 2113-2122
[8] Scalagrino R; Pasquariello; Reumatismo. 1964. 16:333-337.
[9] Cheung MC; Zhao XQl Chait A; Albers JL; Arteriosclerosis, Thrombosis and Vascular Biology. 2001.
21:1320-1326.
Related Compounds:
Folic acid (page 17), Chromium
picolinate (page 25)
Vitamin B6
Description:
A water soluble vitamin and a part
of the vitamin B family. This
vitamin is found in meats, whole
grains, vegetables, nuts and
bananas [1]. Over-consumption of
this vitamin as a supplement may
cause neurological problems [2].
Quick Facts:
Properties: pyridine ring, polar
Molecular Mass: 169.18 g/mol
Figure 1: Pyridoxol Phosphate
Metabolism:
Vitamin B6 has been found to play
a key role in protein metabolism,
neurotransmiter synthesis, hemo-
globlin synthesis and gene
expression. The vitamin has three
different forms: pyridoxine,
pyridoxal, and pyridoxamine,
which are all converted to
Pyridoxal phosphate (PLP). The
active form, PLP, is a coenzyme
which helps with decarboxylation,
transamination, racemization, and
elimination [3].
Important PLP-dependent steps of
the synthesis of neurotransmitters
Dose: 0.72 mg/day | anti-carcinogenic | neuroprotective
include the decarboxylation of 3,4-
dihydroxyphenylalanine (DOPA) to
dopamine, and the conversion of
tryptophan to both nitric acid and
serotonin.
Moreover, since PLP has electron
sink properties, PLP binding enables
the amino acid for further reactions.
PLP also increases hemoglobin's
affinity for oxygen. [4]
Effects:
Deficiency of B6 is uncommon, but borderline deficiency causes anaemia,
reduced immune function, increased risk for cancer (colorectal, pancreatic,
gastric, lung, prostate and breast), and decreased cognitive function [1, 5].
Low synthesis rates of the carbon compounds and subsequently DNA and
RNA synthesis can be attributed to many of the effects of low B6 levels.
7
8
Figure 2: Conversion of Vitamin B6 derivatives to PLP.
Studies have demonstrated that a
deficiency in the B6 vitamin is
correlated with thymic atrophy
and lymphocyte depletion; this is
especially the case for the elderly
[6].
Related Compounds:
Folic acid (page 17)
Moreover, decreased B6 intake in the
elderly has been noted to be
significantly correlated with better
memory performance and cognitive
test scores [6]. Studies have also
demonstrated that B6 intake acts as
a preventative factor against colon
cancer by a reduction of oxidative stress and nitric oxide production [5].
References: [1] Abbot R; British Food Journal 1997. 99(2):43-49.
[2] Bender DA; European Journal of Clinical Nutrition 1989. 43(5); 278-309.
[3] Merril AH; Henderson MJ; Annals of the New York Academy of Sciences 2006. 585:110-117.
[4] John RA; Bhiochem Biophys Acta. 1995. 1248(2):81-96.
[5] Zhang SM; Cook NR; Albert CMl Gaziano M; JAMA 2008. 300(17):2012-2021
[6] Rall LC; Nikbin DVM; Nutrition Reviews 1993. 51(8):217-225.
Vitamin B12
Description:
Vitamin B12 is a water soluble vitamin,
which is a part of the vitamin B family.
It helps with the normal functioning of
the brain and nervous system [1]. It
also plays a role in DNA and fatty acid
synthesis. It is the largest known
vitamin and can be found in liver,
cheese, meat, milk and fortified foods.
It is a common ingredient in energy
drinks. It has low toxicity, but it should
be noted that those who are allergic to
cobalamin should avoid this
supplement. [2]
Quick Facts:
Properties: Polar, contains cobalt
Also contains: 1355.37 g/mol
Figure 1: Vitamin B12 Metabolism:
Vitamin B12 consists of a group of
vitamers that all that contain cobalt
and corrin ring molecules and have
vitamin activity [3]. B12 participates in
isomerase, methyltransferase and
dehalogenase reactions. In humans, the
B12 vitamin consists of: 5’-deoxyaden-
osylcobala-min (AdoB12), and methyl-
cobalamin (MeB12). AdoB12 is a
cofactor of methylmalonyl Coenzyme A
(MUT), a key isomerase in the TCA
cycle. MeB12 is a cofactor of
methyltetrahydrofolate, and homo
cysteine methyltransferase (MTR), the
Dose: 0.72 mcg/day | anti-carcinogenic | anti-inflammatory | antioxidant |
| neuroprotective
9
enzyme that regenerates meth-
ionine from homocysteine [4].
Effects:
This vitamin is reported to boost
energy levels and speed up the
metabolism. Vitamin B12 helps
iron function and it also helps the
body absorb carotene and
vitamin A [6].
Moreover, there is evidence that suggests that B12 promotes absorption of
nutrients in the intestines [6]. In mice, B12 has been seen to act as an anti-
carcinogenic agent [7]. High B12 levels in aging populations has shown to
act as a neuroprotectant [8]. Finally, high dosages of vitamin B12 has been
associated with suppression of T-Cells and the body’s allergic reaction. [9]
Related Compounds: Folic acid (page 17), Beta-carotene (page 33),
Potassium (page 43)
Figure 1: A simplified schematic of the folate-dependent methionine
cycle, vitamin B12 acts as a cofactor. Where, 5-methyltetrahydrofolate
is 5-Ch3-THF, tetrafolate is THF, adenosylmethionine is SAM, S-
adenosylhomosysteine is SAH and Homocysteine is HCY.
10
References: [1] Bottigleiri T; Nutrition Reviews 1996. 54(12)-382-390.
[2] Louis W. S; Victor Hl N Engl J Med. 1965. 272:340-246.
[3] Roth JR; Lawrence JG; Bobik TA; Annual Review of Microbiology. 1996. 50: 137-181
[4] Hines C; Arch Intern Med 1978. 138(4):619-621.
[5] Swanon VL; Wheby MS; Bayless; Am J Pathol 1966. 49:167-191.
[6] [Vilter RW; Will JJ; Wright T; Rullman D; American Journal of Clinical Nutrition 1963. 12:130-142
[7] Ebbing M; Bonaa KH; Nygard Ol Arnesen E; JAMA 2009. 302(19): 2152-2153.
[8] Gonzailez MG, Ascension M; Petrzik K; British Journal of Nutrition 2009. 86: 313-321
[9] Chandra R.K. The Lancelet 1992. 320: 1124-1127.
Vitamin C
Description:
Vitamin C, also called ascorbic acid,
is a water-soluble vitamin. This
vitamin can be attained from citrus
fruit, broccoli and tomatoes.
Vitamin C is needed for the repair
and growth of the body, as it helps
make collagen [1]. This vitamin also
acts as an anti-oxidant [2], a
neuroprotective [3] and anti-
carcinogenic agent [4].
Quick Facts:
Properties: Water soluble
Molecular Mass: 176.12 g/mol
Figure 1: L-Ascorbic Acid
Metabolism:
L-ascorbic acid has many co-factor
functions in the synthesis of
collagen, carnitine, tyrosine, and
neurotransmitters. Carnitine
synthesis’ essential dioxygenases
also require vitamin C for maximal
activity. [1]
This vitamin is also used as a
cofactor for the synthesis of
catecholamine, to convert
dopamine and norepinephrine [2].
Vitamin C also acts as a co-
substrate in peptide amidation and
tyrosine metabolism [3].
Vitamin C acts on dioxygenases by
reducing the active centre metal
ion involved in the previous
Dose: 3.6 mg/day | anti-carcinogenic | anti-inflammatory | antioxidant |
| neuroprotective
Effects:
Deficiency in vitamin C can result in
weaker collagenous structures, which
causes tooth loss, joint pain, bone
and connective tissue disorders, and
slow wound healing, all indicative of
an aging process [1].
Also, since carnitine is required for
fatty acid transport into the mito-
chondria, vitamin C deficiency can
result in fatigue and lethargy. Last,
deficiency can result in mood
changes, attributed deficiency in
dopamine hydroxylation [3].
reactions, attributed to vitamin C’s
redox potential. This ability is
hypothesized to also help with the
gastrointestinal absorption of dietary
iron [4].
11
12
Figure 2: Pathway
for certain Vitamin C
oxidization [2]
in immune cells in high
concentrations, consumed rapidly
when infections occur. Vitamin C is
said to help phagocytes with the
production of lymphocytes [6].
Moreover, Vitamin C acts as an
antihistamine and an anti-
inflammatory agent by preventing
high histamine levels [7]. What’s
more epidemiologic studies in
humans have found evidence that
vitamin C acts as a cancer pre-
venting agent [4].
Many clinical and epidemiological
studies have suggested that vitamin
C could help in the prevention and
maintenance of cardiovascular
disease, cancers, and cataracts [5].
Although Vitamin C has been found
to behave as a pro-oxidant, it
mostly behaves as an antioxidant,
scavenging reactive oxygen species,
reactive oxygen and nitrogen
species. Vitamin C also acts as a co-
antioxidant and pays a large role in
Related Compounds: Vitamin D (page 13), Vitamin E (page 15), Acetyl L-
carnitine (page 23), Chromium picolinate (page 25), Acetylsalicylic acid
(39), Alpha lipoic acid (page 41)
References: [1] Libby P; Aikawa M; Circulation 2002. 105:1396-1398
[2]Carr A; Balz F; Americal Journal of Clinical Nutrition 1999. 69(6): 1086-1107.
[3] Pace A; Antonella S; Mauro P; Bove L; American Society of Clinical Oncology 2003. 21(5): 927-931.
[4] Chen LH; Boissonneault GA; Glauert HP; Anticancer Research. 1988. 8(4):739-48
[5] Valero MP; Fletcher AE; Stavola BL De; The Journal of Nutrition 2002. 132:1299-1306.
[6] Noroozi M; Angerson WJ; Lean ME; American Journal of Climical Nutrition 1998. 67:1210-1218.
[7] Hemila H; British Journal of Nutrition 1991. 67:3-16.
Vitamin D
Description:
Vitamin D is a fat soluble vitamin which can be synthesized by humans in
the skin or it can be obtained from the diet from alfalfa, and different
mushrooms [1].Too much vitamin D intake could be toxic to the body,
however since most of North America is deficient in the vitamin, toxicity is
unlikely [2].
Quick Facts:
Properties: Non-Polar
Figure 1: Calcitrol
Metabolism:
Vitamin D in its consumed and
produced form is inactive, and is
metabolized in the body to
become various derivatives, of
which the most significant is
calcitrol. [1]
More than 50 genes are known to
be regulated by calcitrol. It bonds
with the transcription factor,
vitamin D receptor (VDR), which in
combination with retinoic acid X
receptor modulate transcription in
the nucleus. [1]
Dose: 2.5 IU/day | anti-carcinogenic | antioxidant | insulin-sensitive |
| neuroprotective
13
Vitamin D contributes to the
mechanisms of calcium balance,
immunity, insulin secretion, imm-
unity, blood pressure regulation
and cell regulation. When levels
of calcium are low, the parathyroid
hormone is secreted which
increased the production and
function of calcitrol, which,
through gene regulation, increases
intestinal absorption of dietary
niacin and increases the reabsorp-
tion of calcium in the kidneys [3].
Similarly, vitamin D affects the rate
of insulin secretion when there is
increased insulin demand [4].
There has also been considerable
evidence that vitamin D plays a
role in the suppression of auto-
immune disorders [5]. Research
also indicates that VDR regulates
the expression of renin, in the
angiotensin-renin system, which
contributes to blood pressure
regulation. [6]
Effects: Extreme deficiency in
vitamin D causes Rickets, an illness
characterized by inadequate
mineralization of calcium in weight-
bearing bones. Similarly other
calcium and bone related illnesses
result as a lack of vitamin D.
Increased intake of vitamin D helps
in the maintenance of bones. [4]
Since some of the genes regulated
by vitamin D have been found to
induce cell differentiation through
14
Figure 2: Pathway for the creation of Vitamin D3 in the skin [3]
transcription regulation, its regular
consumption has been shown to
reduce rates of colorectal, breast
and prostate cancer. [7]
Vitamin D’s role in the reninangio-
tension system also contributes to
its ability to maintain hypertension.
[6] Studies have shown that vitamin
D acts as a membrane antioxidant
and acts to suppress autoimmune
disorders. [5]
References: [1] Lehmann B; Meurer M; Dermatologic Therapy 2010. 23:2-12.
[2] Hanley D; Davison S; The Journal of Nutrition 2006. 135:332-337.
[3] Rhoten WB; Bruns EM; Endocrinology 1985. 117(2):674.
[4] Norman AW; Frankel JBl Heldt Am; Grodsky GM; Science 1980. 209:823-825.
[5] Cantorna MT; Mahon BD; Exp Biol Med 2004. 229: 1139-1142.
[6] Li Y[C; Journal of Cellular Biochemistry 2002. 88(2):327-331.
[7] Garland CF; Garland FC; Journal of Public Health 2005. 96:252-261.
Related Compounds: Vitamin C (page 11), Cod liver oil (page 53)
Vitamin E
Description:
Typically found in wheat germ oil
and sunflower oils [1], vitamin E
is a fat-soluble antioxidant.
Recently it has been shown to
have anti-carcinogenic properties
along with its antioxidant
properties [2]. Quick Facts:
Properties: Non-polar
Molar Mass: 430.71 g/mol
Figure 1: α-tocopherol
Dose: 1.44 IU/day | anti-carcinogenic | antioxidant | neuroprotective
Metabolism:
Vitamin E includes four toco-
pherols and four tocotrienols, all
derived from 6-chromanol. Of the
eight types, α-tocopherol, is
preferentially absorbed in humans.
Vitamin E acts as a “chain-
breaking” antioxidant by
preventing the propagation of
free radical reactions involved in
cancer, cardiovascular disease,
diabetes and aging [3].
α-tocopherol has been shown to
regulate expression scavenger
receptors which remove foreign
substances from the body [4].
Moreover, vitamin E has also been
found to regulate the connective tissue
growth factor (GTGF), which promotes
endothelial cell growth. The previous
actions of Vitamin E may be the reason
why Vitamin E also regulates the
activity of protein kinase C (PKC),
which helps muscle growth [5].
α-tocotrienol, another derivative of
vitamin E, has been shown to help with
resistance to stroke-induced brain
injury. The vitamin acts on molecular
checkpoints to protect against glut-
amate and stroke induced neurodeg-
eneration [6].
Effects:
Vitamin E deficiency is known to cause spinocerebellar ataxia, peripheral
neuropathy, ataxia and other neurological and immunological diseases. It’s
neuroprotective effect may be attributed to it’s role as a molecular check
point. [6]
15
Its anti-coagulant role can be
attributed to its role in circulation.
For this reason, Vitamin E cannot
be used with warfarin due to
possibly inhibitory effect caused by
megadoses of vitamin E [7].
Figure 2: The eight forms of vitamin E
16
Related Compounds: Vitamin C (page 11), Coenzyme Q10 (page 27), Beta-
carotene (page 33), Alpha-lipoic acid (page 41), Selenium (page 44)
Research has also indicated that the
anti-carcinogenic action of selenium is
slowed down by a vitamin E deficiency,
especially when the organism was
under high oxidative stress. Vitamin
E’s role as an antioxidant contributes
to it’s role as an anti-carcinogen [2].
References: [1] McLaughlin PJl Weihrauch JL; Journal of the American Dietetic Association 1979. 75(6):647-65.
[2] Burton GW; Traber MG; Annual Review of Nutrition 1990. 10:357-382.
[3] Herrera E; Barbas C; J. Physiol. Biochem 2000. 57(1):43-56.
[4] Brigellus RF; Traber MG; FASEB 1999. 13:1145-1155.
[5] Angelo A; Gysin R; Kempna P; Annals of New York Academy of Sciences 2004. 1031: 86-95.
[6] Kontush A; Schekatolina S; Annals of the New York Academy of Sciences 2004. 1031: 249-262.
[7] Rim[m EB; Stampfer MH; Ascherio A; Giovannuci E; Colditz GA; Willett WC; N Engl J Med 1993.
328:1450-1456.
Folic Acid
Description:
Folic acid is a water soluble B-complex
vitamin, often called Vitamin B9. It is found in
foods such as leafy vegetables, asparagus,
legumes and yeast [1]. Although toxicity from
this vitamin is very rare, an upper limit of 1
mg for men and 0.8 mg for women is
suggested [1]. In the body, it is changed into
folate [2].
Properties: Water soluble
Molecular Mass: 441.4 g/mol
Figure 1: Pyridoxol Phosphate Metabolism:
Vitamin B9 is involved in a reaction
the transfers one-carbon units. The
vitamin acts as an acceptor and a
donor of a carbon unit. Specific
nucleic acid reactions that require this
type of transfer include the synthesis
of DNA from thymidine and purines,
the synthesis of methionine and
consequently, adenosylmethionene,
and finally, it is used for the
methylation of DNA. [2]
Folic acid also plays a role in trans-
ferring single carbon units for amino
acids, for example, changing homo-
cysteine to methionine. Homocysteine
degrades disulfide bridges and lysine
amino acid residues, which degrades
major structural components of the
artery [3]. To carry out this reaction,
NADPH first needs to reduce folic
Dose: 0.01 mg/day | anti-carcinogenic | antioxidant | neuroprotective
acid two times. The pathway
begins with folate (a derivative of
folic acid) which is reduced to
dihydrofolate (DHF) and
tetrahydrofolate (THF), NADPH is
required for this synthesis THF is
the acceptor of the 1-carbon group
[3].
Some reactions of the folic acid
metabolism is heavily reliant on
other reactions. The reaction that
converts methionine to homo-
cysteine requires a folate coenzyme
which requires a enzyme that uses
B12 and another that uses B6 [4].
17
Cancer arises from DNA damage and
inappropriate expression of critical
genes. Since folate plays a role in
nucleotide synthesis and methylation,
folate plays a role in both DNA repair
and expression. Studies have found
that lower folate levels are correlated
to cervical, lung brain pancreas breast
and colorectal cancer. [7]
Folic acid’s role in nucleotide
synthesis and methylation could also
contribute normal brain function. In a
Canadian study, low folate levels were
associated with an increase in short-
term memory problems. Studies have
also found that folic acid may be
associated with Alzheimer's disease
and vascular dementia. [8]
18
Figure 2: The two steps of converting Folate into THF
Effects:
Folate deficiency has been
associated with higher levels of
homocysteine, which is an
indicator of a risk of cardiovascular
disease, since homocysteine con-
tributes to a degradation of arterial
walls. Studies on Finnish males also
found that those with a higher folic
acid intake had a 55% lower risk
for an acute coronary event. [5]
Folate deficiency also causes
anaemia, since folate contributes
to rapid blood cell division [6].
Related Compounds:
Vitamin B1 (page 3), Vitamin B3
(page 5), Vitamin B6 (page 7)
Vitamin B12 (page 9)
References: [1] Chanarin I; Anderson BB, Mollin DL; British Journal of Haematologyi 1958. 4(2):156-166
[2] Stokstad E; Koch J; Physiol Rev 1967. 46:83-116.
[3] Appling DR; FASEB 1991. 5:2645-2651.
[4] Fenech MF; Dreosti IV; Rinaldi JR; Carcinogenesis 1997. 18(7): 1329-1336.
[5] Voutilainen S; Rissanen THl Virtanen J; Lakk T; Circulation 2001. 103:2674-2680.
[6] Morris MS; Jacques PF; Rosenberg IHl Selhub J; American Journal of Clinical Nutrition.85(1):193-200.
[7] Giovannucci E; Stampfer MJ; Colditz GA; JNCI 1993. 85(11)-875-883.
[8] Clake R; Smith DA; Jobst KA; Refsum H; Lesley S; Ueland PM; Arch Neurol. 1998. 55:1449-1455.
N-acetyl cysteine
Description:
N-acetyl cysteine (NAC), the
acetylated variant of L-cysteine, is
a common antioxidant
supplement. It is converted in the
body into metabolites capable of
stimulating glutathione (GSH)
synthesis, promoting detoxifi-
cation and acting directly as free
radical scavengers. NAC is also
often used as a drug for
respiratory illnesses. The structure
of NAC is shown in Figure 1 [1].
cysteine and participates in glutathione (GSH) synthesis.
The functions of NAC in GSH synthesis is highlighted in Figure 2.
Glutathione is synthesized from cysteine and glutamate. NAC functions in
this pathway by supplying the cysteine that’s required for GSH synthesis. As
the GSH concentration in the cell falls, glutamate cysteine ligase is first
released from feedback inhibition to promote the ligation of cysteine and
glutamate. To keep up with the supply of cysteine, exogenously
supplemented NAC is de-acetylated into cysteine. NAC also cleaves the
disulfide bond of plasma cysteine. The free cysteine then enters the cell to
participate in GSH synthesis [2].
Dose: 7.2 mg/day | antioxidant
19
Quick Facts:
Molecular Formula: C5H9NO3S
NAC is an acetylated variant of
amino acid L-cysteine.
Water soluble
Cysteine is found in high protein
foods but NAC is not.
Figure 1: structure of NAC
Metabolism:
The acetyl group on NAC makes it
more water-soluble than cysteine.
Thus it is easily absorbed and
distributed throughout the body
upon oral ingestion. Inside the
body, NAC gets converted to
Effects:
NAC acts as an antioxidant by
scavenging Reactive Oxygen
Species (ROS) in situations where
ROS level is increased. It does so
through 3 mechanisms.
1) increase levels of GSH (one of
the most important antioxidant in
the body) [3].
2) NAC directly reacts with ROS
such as HOCl and H2O2 etc. [4].
3) NAC regulates the expression of
numerous genes through
inhibiting the activation of some
transcription factors. It prevents
apoptosis and promotes cell
survival by activating extracellular
signal-regulated kinase pathway, a
concept useful for treating certain
degenerative diseases. It also
modifies the activity of several
proteins by its reducing activity [5].
References: [1] Image from Wikimedia Commons.
[2] Raftos, J. E., Kuchel, P. W. et al. The International Journal of Biochemitry & Cell Biology. 2007. 33, 9,
1698-1706.
[3] Kerksick, C.; Willoughby, D. J. Int. Soc. Sports. Nutr. 2005. 2(2), 38-44.
[4] Aruoma, O. I.; Butler, J.. et al. Free Radical Biology & Medicine. 1989. 6, 595-597
[5] Zafarullah, M., Li, W. Q., Sylvester, J.; Ahmad, M. Cellular and Molecular Life Scicences. 2003. 60, 6-20
Related Compounds:
L-glutathione (page 21)
20
Figure 2: Functions of NAC in glutathione synthesis.
L-glutathione
Description:
L-glutathione (GSH) is one of the
most important antioxidants in the
body. It is found in almost all cells
in all organisms. It is structurally a
tripeptide and the sulfhydryl (SH)
group on the cysteine serves as a
proton donor and is responsible
for its biological activity [2].
GSH is not absorbed easily by the
gastrointestinal track of humans
upon oral administration. Thus,
intravenous injections of GSH is
preferred to increase intracellular
GSH level [3].
Metabolism:
GSH reduces disulfide bonds formed within cytoplasmic proteins into
cysteine and gets oxidized into glutathione disulfide (GSSG). In glutathione
synthesis, γ-glutamyl-cysteine is first formed from glutamate and cysteine
through γ-glutamyl-cysteine synthetase. Then, glycine is added to the C-
terminal of the γ-glutamyl-cysteine. It is worth noting that NAC is a
precursor in GSH synthesis by serving as a reservoir for cysteine.
Additionally, glycolysis pathway is also involved in step 17 of GSH synthesis.
Refer to Figure 2 for a detailed diagram of GSH synthesis [4].
Dose: 0.36 mg/day | antioxidant
21
Quick Facts:
Molecular Formula: C10H17N3O6S
Linear tripeptide make of L-
glutamate, L-cysteine and glycine.
Most important antioxidant
Water-soluble
Found in almost all cells with
highest concentration in liver cells.
Figure 1: structure of GSH [1]
Effects:
GSH scavenges free radicals and
other ROS (e.g., hydroxyl radical,
lipid peroxyl radical, peroxynitrite,
and H2O2) directly. Indirectly, it
reduces ROS through enzymatic
reactions by donating electrons
and oxidizing to GSSG [5].
Additionally, glutathione peroxi-
dase catalyzes the GSH-dependent
reduction of H2O2 and other
peroxides. GSH also assists in the
storage and transport of cysteine,
the synthesis of leukotrienes and
prostaglandins, the regulation of
intracellular redox, signal
transduction and expression,
apoptosis, immune response, and
cytokine production [5]. Lastly, the
GSSG/GSH ratio rises with aging in
the liver, kidney, and brain [6].
References: [1] Image from Wikimedia Commons.
[2] Lu, S. C. Curr. Top. Cell Regul. 2000. 36:95-116.
[3] Witschi, A.; Reddy, S.; Stofer, B.; Lauterburg, B. H. European Journal of Clinical Pharmacology, 1992.
43, 6, 667–9.
[4] Griffith, O. W. Free Radic. Biol. Med. 1999. 27, 922-935.
[5] Fang, Y. Z.; Yang, S.; Wu, G. Nutrition 2002. 18, 872-879
[6] Jones, D. P. Methods Enzymol. 2002. 348:93-112
Related Compounds: N-acetyl cysteine (page 19), Alpha lipoic acid (page
41)
22
Figure 2: GSH synthesis and utilization in animals. [2]
Acetyl L-Carnitine
Description:
Acetyl L-carnitine (ALCAR) is a
common dietary supplement that
helps the body turn fat into
energy. It is an acetyl form of L-
carnitine with the acetyl group
replacing the hydroxyl group. It is
also used as a medication for
various neurological disorders like
Alzheimer's disease and age-
related memory loss due to its
ability to cross the blood-brain
barrier. [1]
Endogenous ALCAR is synthesized intra-mitochondrially in many tissues
including brain, liver, heart, kidney and muscle. It is formed by carnitine
acetyltransferase that combines L-carnitine with an acetyl group from CoA.
Once formed, ALCAR is transported across the inner mitochondrial
membrane by carnitine acetyltranslocase (CarAT) into the cytoplasm to
serve as a source of acetyl groups. It also provides acetyl groups for the
production acetylcholine, which is a neurotransmitter. It is worth noting that
Vitamin C is essential for the synthesis of ALCAR precursor L-carnitine.
Refer to Figure 2 [3].
Dose: 14.4 mg/day | antioxidant | neuroprotective
23
Quick Facts:
Molecular Formula: C9H17NO4
An acetylated form of L-carnitine.
Naturally in plants and animals.
Water soluble and can cross the
blood-brain barrier.
Figure 1: structure of ALCAR
Metabolism:
When ALCAR is exogenously
administered, it is rapidly removed
from the plasma and taken up by
many tissues in the body such as
kidney, heart, brain and liver. [2]
Effects:
ALCAR functions physiologically as
transport between the
mitochondria and cytoplasm for
long-chain fatty acid. Thus it plays
a role in cellular energy
production and in removing toxic
accumulation of fatty acids from
mitochondria [4].
ALCAR especially benefits the
brain because it promotes the
production of neurotransmitter
acetylcholine and its ability to
cross the blood-brain barrier when
supplemental exogenously. It has
been shown to clinically benefit
cognitive abilities, memory and
mood [5].
In anti-aging research, ALCAR has
been shown to play a role in
preventing mitochondrial damage.
It was shown that when given to
old mice, ALCAR greatly improves
mitochondrial function. with the
mice exhibiting phenotypes of
increased short term memory and
cognitive function. When given in
high doses, ALCAR also lowered
oxidative stress in mice [6].
References: [1] Image from Wikimedia Commons.
[2] Rebouche C. J. Ann. N. Y. Acad. Sci. 2004, 1033, 30–41.
[3] Hendler, S.S. & Rorvik, D., eds. Acetyl-L-carnitine, L-carnitine. PDR for Nutritional Supplements.
Montvale, Medical Economics Company, Inc., 2001, p 9-11, 255-259
[4] Carta A, Calvani M, Bravi D, Bhuachalla SN. Ann NY Acad Sci. 1993, 95, 324-326.
[5] White HL, Scates PW. Neurochem Res. 1990,15, 597-601.
[6] Hagen, T. M; Ames, B. N et al. PNAS. 2002. 99, 4, 1870-5
Related Compounds:
Vitamin C (page 11), Alpha-lipoic
acid (page 41), Cod liver oil (page
53), Flax seed oil (page 55).
24
Figure 2: functions of ALCAR as
a reservoir for acetyl groups.
Chromium Picolinate
Description:
Chromium picolinate is a dietary
supplement used to treat
chromium deficiency. Chromium is
a trace mineral found in foods like
brewer’s yeasts and eggs etc. It is
the active ingredient in Glucose
Tolerance Factor (GTF), which
plays a role in controlling blood
glucose level by enhancing the
function of insulin [2].
the active component of the hormone-like Glucose Tolerance Factor (GTF).
The GTF complex is composed of one trivalent chromium surrounded by
two nicotinic acid (Vitamin B3) and amino acids, shown in figure 2 [3]. GTF
works as a cofactor of insulin because it enhances the function of insulin.
After a meal, as blood glucose levels begin to increase, insulin is secreted
from the pancreas. Insulin lowers blood glucose level by promoting glucose
update into the cell. It is believed that GTF plays a role in enhancing
insulin’s function by initiating the attachment of insulin to the insulin
receptor. GTF and insulin also promote the use of amino acids for protein
synthesis and the improvement in phagocytic ability of white blood cells [4].
Chromium may also play a role in cholesterol metabolism and nucleic acid
metabolism.
Dose: 1.44 mcg/day | insulin-sensitive
25
Quick Facts:
Molecular Formula: Cr(C6H4NOs)3
It is used to supply the trace
mineral chromium in the body
This supplement has been
advertised to promote weight loss
and muscle building.
Figure 1: structure of chromium
picolinate [1].
Metabolism/ function:
Chromium picolinate is a more
bioavailable form of chromium
because it is more easily absorbed
than the mineral salt form. Vitamin
C is thought to promote
chromium absorption. In natural
foods, chromium is found in its
biologically active form, which is
Related Compounds:
Vitamin B3 (page 5), Vitamin C
(page 11)
Effects:
Chromium picolinate helps to
maintain the body’s chromium
level to avoid chromium
deficiency. However, the amount
of chromium required by the body
is not yet known [5].
Since insulin has an anabolic effect
on skeletal muscle through
promoting protein synthesis,
Chromium is advertised to
promote muscle building, though
research has not shown this
effect[4]. It is claimed that
chromium picolinate can increase
average life span based on some
limited animal data. A study by Dr.
Evans showed that high levels of
chromium picolinate increased
longevity in rat [6]. Overall, this
supplement is a very controversial
in terms of the efficacy of its
advertised effects.
References: [1] Image from Wikimedia commons.
[2] Tuman, R. W; Doisy, R. J. Diabetes. 1977, 26, 9, 820-826.
[3] Steele, N. C., Althen, T. G.; Frobish, L. T. J. Anim. Sci. 1997, 45, 1341-1345.
[4] Mertz, W. Physio. Rev. 1969, 49, 2.
[5] Stearns, D. M. Biofactors, 2000, 11, 3, 149–62.
[6] Evans, G. W. J. Inorganic Biochemistry, 1992, 46, 4, 243-250.
26
Figure 2: The structure of
Glucose Tolerance Factor
(GTF). The trivalent chromium
forms a complex with two
nicotinic acid (Vitamin B3)
and three amino acids. The
amino acid moieties,
cysteine, glutamic acid and
glycine, render the salt water
soluble. [3]
Coenzyme Q10
Description:
Coenzyme Q10, or ubiquinone, is
a naturally-occurring compound
found in almost very cell in the
body. It plays a role in aerobic
energy production in the form of
ATP as it is a part of the electron
transport chain (ETC) in the inner
mitochondrial membrane.
Coenzyme Q10 is often taken as a
supplement with cardiovascular
benefits and anti-aging properties.
Coenzyme Q10 is synthesized in the mitochondria and endoplasmic
reticulum from tyrosine (or phenylalanine) and acetyl-CoA. Tyrosine is
converted to hydroxybenzoate through multiple steps while acetyl-CoA is
converted to farnesyl,-PP (FPP). Afterwards, hydroxybenzoate and FPP are
combined to from Coenzyme Q10 [3].
Coenzyme Q10 functions as an electron carrier in the electron transport
chain. In ETC, electrons are passed through a series of compounds starting
from NADH and ends with oxygen in order to create a proton gradient
across the inner mitochondrial membrane. CoQ10 shuttles electrons from
enzyme complex I and enzyme complex II to complex III in this process.
Refer to Figure 2 for the process of electron transport chain [4].
Dose: 0.44 mg/day| antioxidant
27
Quick Facts:
Molecular Formula: C59H90O4
Oil soluble
Present in most eukaryotic cells,
primarily in the mitochondria
It is part of the electron transport
chain (ETC)
Figure 1: structure of Coenzyme Q10 [1].
Metabolism:
Exogenous Coenzyme Q10 is
absorbed from the small intestinal
tract. The absorption follows the
same process as that of lipids and
its uptake mechanism is similar to
that of Vitamin E [2].
Effects:
Antioxidant – since CoQ10 is an
energy carrier, it gets oxidized or
reduced easily, serving as an anti-
oxidant. CoQ10 also inhibits lipid
peroxidation by preventing the
formation of peroxyl radicals. It
reduces the level of perferryl
radicals, thus inhibiting both the
initiating and propagation of lipid
peroxidation. CoQ10 can also
effectively regenerate vitamin E
from α-tocopheroxyl radicals [5].
Anti-aging – CoQ10 is often used
in skincare products to slow down
cutaneous aging. Its anti-aging
mechanism is based on lowering
oxidative stress and slowing down
mitochondrial decline. It has been
to shown to prolong lifespan in
C.elegans and rats [6].
References: [1] Image from Wikimedia Commons.
[2] Ochiai A.; Itagaki S.; Kurokawa T.; Kobayashi M.; Hirano T.; Iseki K. Yakugaku Zasshi . 2007, 127, 8,
1251–4.
[3] Bentinger, M.; Tekle, M.; Dallner, G. Biochem. Biophys. Res. Commun. 2010, 396, 1, 74–9.
[4] Forster, M. J. et al. Free Radic. Biol. Med. 2006, 1, 41, 480-7
[5] Tappel, A. L. et al. Clinical Biochemistry. 2000, 33, 4, 279-284.
[6] Furukawa, S. et al. Mech. Ageing Dev. 2004, 125, 1, 41-6.
Related Compounds:
Vitamin E (page 15)
28
Figure 2: Eukaryotic electron transport chain.
Inner membrane space
Coenzyme Q10
Dehydroepiandrosterone
Description:
Dehydroepiandrosterone (DHEA)
is an endogenous hormone made
mostly by the adrenal gland in the
body. It serves as precursor for
male and female sex hormones
(androgens and estrogens
respectively). DHEA is widely used
to treat systemic lupus
erythematosus, adrenal deficiency,
and depression. It has been shown
that DHEA levels decreases with
age [2].
Dose: 0.15 mg/day
29
Quick Facts:
Molecular Formula: C19H28O2
19-carbon endogenous steroid
hormone.
oil soluble
Mainly produced by the adrenal
gland and it is the most abundant
circulating steroids.
Figure 1: structure of DHEA [1].
Metabolism/ synthesis:
DHEA is converted in the body to
become sex hormones, androgens
and estrogens. Like all steroid
hormones, DHEA is synthesized
from cholesterol. Refer to Figure 2.
for DHEA synthesis [2].
Effects/ functions:
Systemic lupus erythematosus – SLE is an autoimmune disorder where the
body’s immune system attacks its own tissue. DHEA supplementation has
been to shown to improve the quality of life for people with lupus,
enhancing mental function and boosting bone mass.
Adrenal insufficiency – with adrenal insufficiency, the adrenal gland does
not make enough DHEA or cortisol. DHEA supplementation has been
shown to improve mood, fatigue and well-being [3].
Effects:
Natural DHEA levels peak in early
childhood and fall as age
increases. This observation
suggests that DHEA supple-
mentation slows the aging
process. Studies have shown that
DHEA supplementation improves
immune functions by increasing
levels of interleukin-2. It also
showed to increase insulin growth
factor (IGF) that regulates blood
glucose metabolism. It also helps
to protect bone mineral density in
women. Although all these
benefits suggest the anti-aging
properties of DHEA, other research
have shown that no differences
were seen for people who took
DHEA and those who did not in
terms of insulin sensitivity, body
composition and physical
performance. Thus the anti-aging
effects of DHEA remain
inconclusive [4].
References: [1] Image from Wikimedia commons.
[2] Schulman, Robert A., Dean, Carolyn. DHEA is a common hormone produced in the adrenal glands,
the gonads and the brain. Solve it with supplements. New York City, Rodale, Inc., p.100.
[3] Crosbie, D; Black, C, McIntyre, L, Royle, PL, Thomas, S. Dehydroepiandrosterone for systemic lupus
erythematosus. Cochrane database of systematic reviews,2007, 4.
[4] Arlt, W. 2004, 18, 3,363–80.
Related Compounds:
none
30
Figure 2: DHEA synthesis and its related hormones
Melatonin
Description:
Melatonin is an endogenous
hormone produced by the pineal
gland in the brain in response to
environmental light/dark cycles
[2]. Its main function is to help
regulate other hormones and to
maintain the body’s circadian
rhythm. Melatonin levels
decreases with increasing age.
excreted to bile as hydroxymelatonin conjugated with sulfate or
glucuronide. The production of melatonin is light dependent. During the
day when light is abundant, the level of melatonin is decreased, while at
night, melatonin level is increased, promoting sleep. Refer to Figure 2 for
melatonin synthesis [3].
Dose: 0.01 mg/day | antioxidant
31
Quick Facts:
Molecular Formula: C13H16N2O2
A hormone produced by the pineal
gland in the brain.
Water soluble
It regulates body’s circadian rhythm
Figure 1: structure of melatonin [1].
Metabolism:
Melatonin is synthesized from L-
tryptophan. Tryptophan circula-
ting in the blood is taken up by
pinealoctyes and converted to
melatonin. Melatonin is then
metabolized by the liver and
Effects:
Circadian rhythm – The main function of melatonin is to regulate the
sleep-wake cycle. At night when melatonin level is high due to lack of
night, melatonin promotes sleep through chemically causing drowsiness.
Melatonin acts on the target cell mostly indirectly through its G-protein
coupled receptors that modulate several intracellular messengers such as
cAMP, cGMP and [Ca2+] [4].
Melatonin is also a powerful
antioxidant as it can easily cross
the blood-brain barrier and cell
membrane. It can directly
scavenge OH, NO and oxygen
radicals. Interestingly, once
melatonin is oxidized upon
reacting with free radicals, it can
not get reduced again. In the GI
track, melatonin mostly functions
to deal with stress such as irritants
and toxins [5]. Melatonin has been
implicated in aging because its
level decreases with age [6].
References: [1] Image from Wikimedia commons.
[2] Sudgen, D. Experientia, 1989, 45, 922-931.
[3] Bubenik, G. A. et al. J Physiol Pharmacol. 2007, 6, 23-52.
[4] Moore, R. Y. Annu Rev Med. 1997, 48, 253-266.
[5] Calvo, J. R. et al. Biol. Signals. Recept. 2000, 9, 134-59.
[6] Bondy, S. C. et al. J. Pineal Res. 2004, 36, 165-70.
Related Compounds:
none
32
Figure 2: Melatonin
synthesis [3].
Beta-Carotene
Description:
Beta-carotene is a pigment that can be found in plants and fruits,
particularly those that are orange and yellow, such as carrots and squash
[6]. Beta-carotene is the biological precursor to vitamin A, which is
biologically useful to the body.
Beta-carotene is cleaved symmetrically into 2 retinal molecules by beta-
beta-carotene-15,15’-dioxygenase in the presence of alpha-tocopherol (Fig.
2)[3,4]. Retinal can then be converted to other forms of vitamin A. Retinal
can be converted into a transportable form of vitamin A, retinol, by retinol
dehydrogenases and alcohol dehydrogenases [5]. Retinol is also known as
the alcohol form of vitamin A. Another form of vitamin A is retinoic acid,
which also acts as an important signalling molecule and hormone in
vertebrate animals. Retinal is converted to retinoic acid by retinal oxidase
[5].
Dose: 50.0 IU/day | antioxidant
33
Quick Facts [1]:
Chemical Formula: C40H56
Molecular Weight: 526.8726 g/mol
Properties: Hydrophobic, non-polar
Figure 1: Beta-carotene
Metabolism:
Beta-carotene can be found
readily available from natural
sources and will be converted to
vitamin A for biological processes.
It is first absorbed by the
lymphatic system of the body and
the absorption depends on dietary
fat and bile concentration in the
gastrointestinal tract [1].
Effects:
The body absorbs 22% of dietary
beta-carotene into the lymphatic
system which is then transferred
into the liver [1]. Beta carotene can
act as an antioxidant by
quenching singlet oxygen and
other radicals [2]. To be cleaved
into retinal, the process requires
alpha-tocopherol, also known as
vitamin E [4].
Retinal, retinol, and retinoic acid,
compounds that have vitamin A
activity, also known as retinoids
have hormone-like effects in
developing bone. They also act as
immunostimulants and are
essential for vision and
reproduction. [5]
References: [1] National Centre for Biotechnology Information. PubChem: Beta Carotene.
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=573 (accessed Mar 19, 2012).
[2] Sies, H.; Stahl, W. Am J Clin Nutr. 1995. 62: 1315S-1321S.
[3] Biesalski, H.K.; Chichili, G.R.; Frank, J.; von Lintig, J.; Nohr, D. Vitam Horm. 2007. 75: 117-30.
[4] Lakshman, M.R. J Nutr. 2004. 134: 241S-245S.
[5] Napoli, J.L.; Race, K. R. J Biol Chem. 1988. 263: 17372-7
[6] United Sates Department of Agriculture. Agricultural Research Service: Nutrient lists.
http://www.ars.usda.gov/Services/docs.htm?docid=17477 (accessed Mar 19, 2012).
Related Compounds:
Vitamin B12 (page 9), Vitamin E
(page 15), Gingko biloba (page
51)
34
Figure 2: Cleavage of beta carotene into retinal.
Alpha-tocopherol + beta-beta-carotene-15,15’-dioxygenase
Bioflavonoids
Description:
Bioflavonoids are a class of plant
secondary metabolites, organic
compounds which do not
contribute directly to the growth,
development, or reproduction of
plants [9]. Secondary metabolites
are often used for medicines,
flavourings, or recreational drugs.
Bioflavonoids are comprised of
three major classes: flavonoids,
isoflavonoids, and neoflavonoids.
The classes can be further
branched into flavanols, flavones,
flavanones, catechins, antho-
cyanidins, isoflavones, dihydro-
flavonols, and chalcones [2].
35
Quick Facts:
Major groups: flavonoids,
isoflavonoids, and neoflavonoids,
derived from 2-phenylchromen-4-
one (flavones), 3-phenylchromen-
4-one and 4-pneylcoumarin,
respectively [1]
Properties: Hydrophobic, polar
Figure 1: general chemical structures
of flavonoids (A), isoflavonoids (B),
and neoflavonoids (C). [1]
Metabolism:
Many flavonoids occur naturally as flavonoid glycosides (FG), which are
absorbed into the small intestine epithelial cells by sodium-dependent
glucose transporter 1 (SGLT1)(Fig.2)[4]. The efficiency of this absorption is
suppressed by the efflux of FG by apical transporter multidrug resistance-
associated protein 2 (MRP2)[5]. FG could also gain entry to the intestinal
epithelial cells by being hydrolyzed by broad-specific β-glucosidase
enzyme (BSβG)[7]. Lactase phloridzin hydrolase (LPH) was found to also be
able to hydrolyze FGs in the brush border of the small intestine [6]. A
study subject ingested an onion meal with quercetin glucosides and
quercetin was found in plasma afterwards, suggesting that FGs are
processed before entering the blood plasma for circulation [8].
A
B C
Dose: 4.32 mg/day | anti-coagulant | anti-inflammatory | antioxidant
Effects:
Bioflavonoids have been shown to
have antibacterial, antiviral, anti-
inflammatory, anti-allergic, and
vasodilatory effects. It inhibits lipid
peroxidation and platelet
aggregation. Generally, they also
act as antioxidants, free radical
scavengers and chelators of
divalent cations. As antioxidants,
they inhibit the initiation stage of
lipid peroxidation and/or
accelerate the termination stage to
help prevent atherosclerosis and
cancer. Regular consumption of
flavonoids in red wine, dark
chocolate, or green tea have been
proposed to decrease risk of
coronary heart disease.
References: [1] IUPAC. Goldbook: Flavonoids. http://goldbook.iupac.org/F02424.html (accessed Mar 19, 2012).
[2] Cook, N.C.; Samman, S. J Nutr Biochem.1995. 7: 66-76.
[3] Walle, T. Free Radical Biol & Med. 2004. 7: 829-837.
[4] Hollman,P.C.H. et al. M.B. Am J Clin Nutr. 1995. 62: 1276-1282.
[5] Walgren, R.A.; Karnaky Jr. K.J.; Lindenmayer, G.E.; Walle, T. J Pharmacol Exp Ther. 2000. 294: 830–
836.
[6] Day, A.J. et al. FEBS Lett. 2000. 468: 166–170.
[7] Day, A.J. et al. G. FEBS Lett. 1998. 436: 71–75.
[8] Moon, J. H.; Nakata, R.; Oshima, S.; Inakuma, T.; Terao, J. Am J Physiol Regulatory Integrative Comp
Physiol. 2000. 279: R461–R467.
[9] Manach, C.; Morand, C.; Demigné, C.; Texier, O.; Régérat, F.; Rémésy, C. FEBS Lett. 1997. 409: 12-16.
Related Compounds:
Rutin (page 38), Gingko biloba
(page 51), Green tea extract
(page 59)
36
Figure 2: Pathways of
transport and metabolism of
flavonoid glucosides (FG).
Rutin
Description:
Rutin is the flavonoid glycoside
form of the flavonol quercetin. It is
also known as quercetin
rutinoside. It can be found
naturally in buckwheat, asparagus,
mulberry, onions, cranberries,
green tea, and the Brazilian fava
d’anta fruit.
Metabolism:
Similar to the metabolism of flavonoids outlined on page 35, the
metabolism of rutin, a flavonoid glucoside, follows the same process. In
comparison to quercetin, rutin is absorbed more slowly than its aglycone
counterpart because it must first be hydrolyzed by the gastrointestinal tract
for uptake. Quercetin is hydrolyzed to quercetin glucuronide and/or
sulphate conjugates by β-glucuronidase/quercetin-3-sulfate 3’-
sulfotransferase, respectively for transport in the blood plasma [6].
Dose: 0.72 mg/day | anti-coagulant | anti-inflammatory | antioxidant
37
Quick Facts:
Chemical Formula: C27H30O16
Molecular weight: 610.5175 g/mol
Properties: Hydrophobic, polar
Figure 1: Structure of rutin.
Effects:
Rutin and quercetin have been shown to be able to inhibit platelet
aggregation [3][4]. They also have anti-inflammatory activity [5]. Like other
flavonoids, rutin and quercetin act as antioxidants and free-radical
scavengers. In addition, they can inhibit cytotoxicity of oxidized low-
density lipoprotein [1].
References: [1] Walle, T. Free Radic Biol & Med. 2004. 7: 829-837.
[2] Manach, C.; Morand, C.; Demigné, C.; Texier, O.; Régérat, F.; Rémésy, C. FEBS Lett. 1997. 409: 12-16.
[3] Cook, N.C.; Samman, S. J Nutr Biochem.1995. 7: 66-76.
[4] Navarro-Núñez, L.; Lozano, M. L.; Palomo, M.; Martínez, C.; Vicente, V.; Castillo, J.; Benavente-García,
O.; Diaz-Ricart, M.; Escolar, G.; Rivera, J. J Agric Food Chem. 2008. 56: 2970-6.
[5] Guardia, T.; Rotelli, A. E.; Juarez, A.O.; Pelzer, L. E. Farmaco. 2001. 56: 683-7.
[6] Day, A. J.; Mellon, F.; Barron, D.; Sarrazin, G.; Morgan, M. R.; Williamson, G. Free Radic Res. 2001. 35:
941-52.
Related Compounds:
Bioflavonoids (page 35), Green tea extract (page 59)
38
Figure 2: Conversion of quercetin to quercetin glucuronide (A) and
quercetin 3-sulfate (B).
A
B
Acetylsalicylic acid
Description:
Acetylsalicyclic acid (ASA),
also known as aspirin, is a
drug that is often used as an
analgesic to relieve minor
pain and has anti-
inflammatory and antipyretic
effects to reduce fever [1]. It
was discovered in August of
1897, by German chemist
Felix Hoffmann in a
pharmaceutical laboratory of
Friedrich Bayer & Co [7].
Salicylic acid may be
consumed in one’s diet and
can also be synthesized
endogenously [3].
Metabolism:
Acetylsalicyclic acid acts in the arachidonic acid cascade by restricting the
conversion of fatty acid into prostaglandin G2, and subsequently
thromboxane A2, by irreversibly inactivating the cyclooxygenase enzyme
COX-1 and alternating the enzymatic activity of cyclooxygenase enzyme
COX-2 (Fig. 2)[8]. Prostaglandins are a group of lipids that are typically
more than 20 carbons long and have a 5-carbon ring. They act as
autocrine or paracrine hormones that control pain transmission to the
brain, regulation of temperature, and inflammation. Downstream of
prostaglandins are thromboxanes A2 and prostacyclin. It has been found
that thromboxanes A2 has an effect in platelet function and low doses of
aspirin will increase bleeding time and reduce thrombosis [8].
Dose: 2.50 mg/day | anti-coagulant | anti-inflammatory
39
Quick Facts:
Chemical Formula: C9H8O4
Molecular weight: 180.157 g/mol
Properties: Hydrophobic, polar
Figure 1: Chemical structure of ASA
Effects:
ASA has mostly been known as a
medication for pain and fever, as
mentioned earlier. Aspirin also has
the effect of inhibiting platelet
aggregation [2]. With intake of
regular low doses, it can help
prevent heart attacks and
has been recommended for people
with known cardiac disease to
prevent strokes. In individuals
without cardiovascular diseases,
there is little benefit of low doses of
aspirin and increased risk of
hemorrhagic stroke and
gastrointestinal bleeding [4]. More
recently, research suggests that
aspirin could play a role in cancer
prevention [6].
Aspirin may inhibit the absorption
of vitamin C, and breakdown fatty
acids such as those in cod liver oil
[5].
References: [1] National Centre for Biotechnology Information. PubChem: Aspirin.
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2244 (accessed Mar 21, 2012).
[2] Lewis, H. D. Jr. et al. N Engl J Med. 1983. 309: 396-403.
[3] Paterson, J. R. et al.. J Agric Food Chem. 2008. 56:11648-52.
[4] Antithrombotic Trialists' (ATT) Collaboration, Baigent, C. et al. Lancet. 2009. 373: 1849-60.
[5] Loh, H. S.; Watters, K.; Wilson, C. W. J Clin Pharmacol. 1973. 13: 480-6.
[6] Sneader, W. BMJ. 2000. 321:1591-4.
[7] Ghooi, R. B.; Thatte, S. M.; Joshi, P. S. Med Hypotheses. 1995. 44:77-80.
Related Compounds:
Vitamin C (page 11),
Magnesium (page 46), Ginger
(page 49), Cod liver oil (page 53),
Flax seed oil (page 55)
40
Prostaglandin G2
Arachidonic acid
Thromboxane A2
Figure 2: Arachidonic acid cascade and aspirin [8].
Prostacyclin
cyclooxygenase
Aspirin
Metabolism:
Research suggests that LA is taken up by monocarboxylate and Na+-
dependent multivitamin transporters [3]. After gastrointestinal uptake, LA
accumulates in skeletal muscle, the liver, and the heart. In vivo studies
reveal that LA is subject to β-oxidation is rapidly reduced to dihydrolipoic
acid (DHLA) [3]. Research has found that the most common metabolites
of LA found in the body after ingestion include bisnorlipoic acid,
tetranorlipoic acid, 6,8-bismethylthio-octanoic acid, 4,6-bismethylthio-
hexanoic acid, and 2,4-bis-methylthio-butanoic acid, which suggests that
LA is metabolized through β-oxidation and S-methylation.
Alpha-lipoic Acid
Description:
Alpha-lipoic acid (LA) is a chiral
organosulfur compound derived
from octanoic acid [1]. It can exist
as R-(+)-lipoic acid (RLA) and S-(-
)-lipoic acid (SLA), but only the R
enantiomer is found in nature,
biosynthesized by the cleavage of
linoleic acid and acting as a
coenzyme of several enzymes [1].
It can be found readily available as
a nutritional supplement at local
pharmacies.
Effects:
In vitro studies have found LA, and its reduced form DHLA, to be
antioxidants and radical scavengers [7]. LA and DHLA create a potent
redox couple which make them potent antioxidants. It has been found that
DHLA and LA scavenge a variety of reactive oxygen species. Both DHLA
and LA may scavenge hydroxyl radicals and hypochlorous acid, and LA will
terminate singlet oxygen [3]. LA also has anti-inflammatory effects by
inhibiting the NFκB pathway [7].
Dose: 0.72 mg/day | antioxidant | anti-inflammatory
41
Quick Facts:
Chemical Formula: C8H14O2S2
Molecular weight: 206.326 g/mol
Properties: Hydrophobic, non-polar
Figure 1: R-enantiomer of alpha-
lipoic acid.
DHLA is also able to regenerate
other endogenous antioxidants
such as vitamins C, E, and
glutathione (GSH) [5]. LA and
DHLA are also metal-chelators of
Cu2+, Zn2+, and Pb2+[6]. DHLA
prevents Cu(II)-mediated oxidation
of LDL and chelation of iron and
copper in the brain, reducing the
risk of Alzheimer’s by decreasing
the free radical damage [2].
LA has been proposed to
modulate GSH levels through
transcription factor Nrf2, reversing
the age-related decline of GSH
levels caused by deficits in ARE-
mediated gene transcription [3].
LA can also activate protein kinase
signalling pathways to phos-
phorylate Nrf2, promoting the
transcription of genes in response
to Phase II detoxification (fig. 2)[3].
References: [1] National Centre for Biotechnology Information. PubChem: Thioctic acid.
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6112 (accessed Mar 22, 2012).
[2] Bush, A. I. Neurobiol Aging. 2002. 23: 1031–1038.
[3] Shay, K. P.; Moreau, R. F.; Smith, E. J.; Smith, A. R.; Hagen, T. M. Biochim Biophys Acta. 2009. 1790:
1149-60.
[4] Raddatz, G.; Bisswanger, H. J Biotechnol. 1997. 58:89-100.
[5] Biewenga, G. P.; Haenen, G.R.; Bast, A. Gen Pharmacol. 1997. 29: 315–331.
[6] Ou, P.; Tritschler, H. J.; Wolff, S. P. Biochem Pharmacol. 1995. 50: 123–12.
[7] Packer, L.; Witt, E. H.; Tritschler, H. J. Free Radic Biol Med. 1995. 19: 227–250.
Related Compounds:
Vitamin C (page 11), Vitamin E (page 15), L-gluathione (page 21), Acetyl
L-carnitine (page 23), Zinc (page 45), Cod liver oil (page 53)
42
Figure 2: Pathway of activating Phase II detoxification response [3].
LA Keap1
SH HS
Keap1
SH HS
Protein kinase
Nrf2
ARE Phase II genes
P
Potassium
Description:
Potassium is an alkali metal that
rapidly oxidizes in air, like sodium.
Potassium occurs naturally as ionic
salts and in plants [1]. Deficiency of
potassium
43
Quick Facts:
Chemical properties: alkali metal
Molecular Mass: 39.10 g/mol
Metabolism:
Potassium is an important electrolyte in the body for carbohydrate
metabolism, helping to convert glucose to glycogen in the liver [2]. It also
participates in the synthesis of protein from amino acids [3]. Magnesium
helps maintain potassium in the cell, but sodium-potassium balance is
controlled stringently [2].
Dose: 0.36 mg/day | insulin-sensitive
Effects:
Potassium ions are crucial for
nerve impulse transmission in
humans and animals [1].
Highly selective potassium
ion channels are crucial for
hyperpolarization of neurons,
in order to conduct an action
potential [1]. Research has
suggested that intake of
greater than 4.7 g of potassium per day is
related to vasodilation in humans and
animals, and potassium has an effect in
insulin secretion and action [3]. In a study
of spontaneous hypertensive rats, it was
found that oral administration of
potassium overload reduced blood
pressure, improved glucose metabolism
and enhanced insulin sensitivity [2].
References: [1] Minor, D. L. Jr. Curr Opin Struct Biol. 2001. 11: 408-14.
[2] Slonim, A. D.; Pollack, M. M. Pediatric critical care medicine: Potassium. Lippincott Williams &
Wilkins: Philadelphia, 2006.
[3] National institute of Health. MedLine Plus: Potassium in Diet.
http://www.nlm.nih.gov/medlineplus/ency/article/002413.htm (accessed Mar 23, 2012).
Related Compounds: Vitamin B12 (page 9), Magnesium (page 46)
of potassium may lead to hypokalemia, muscle weakness, decreased reflex
responses, respiratory paralysis, and cardiac arrthymia [2]. Potassium can
typically be consumed through red meat, chicken, fish, potatoes, squashes,
dried apricots, as well as nuts [3].
Selenium
Description:
Selenium is a non-metal that has
been recognized to be essential to
the diet of humans [3]. Selenium can
be found in vegetables, fish, shellfish,
red meat, grains, eggs, chicken, and
44
Quick Facts:
Chemical properties: non-
metal
Molecular Mass: 78.96 g/mol
Metabolism:
Selenium is an essential component of the catalytic centre of glutathione
peroxidase, which reduces hydroperoxides and is involved in antioxidant
protection of cells [1]. Other selenoenzymes and specific selenoproteins,
such as iodothyronin 5’-deiodinase and thioredoxin reductase, all contain
selenium to be functional enzymes. It is important to note that
selenoenzymes and selenoproteins contain selenium in the form of
selenocysteine (SeCys) [1].
Dose: 1.08 mg/day | antioxidant
Effects:
The selenoenzymes, also called
antioxidant enzyme, play a role
in preventing cell damage and
may prevent certain cancers
and cardiovascular diseases [2].
Together with vitamin E, research has
suggested the two can work together
in cancer prevention [1]. Studies have
suggested that selenium intake has a
relationship with prevention with
cancer but selenium deficient diets
have not been found to cause cancers
[1].
References: [1] Combs, G. F. Jr.; Gray, W. P. Pharmacol & Therapeutics. 1998. 79: 179-192.
[2] National institute of Health. MedLine Plus: Selenium in Diet.
http://www.nlm.nih.gov/medlineplus/ency/article/002414.htm (accessed Mar 24, 2012).
[3] McConnell, K. P.; Smith, J. C. Jr.; Higgins, P. J.; Blotcky, A. J. Nutr Res. 1981. 1: 235-241.
Related Compounds:
Vitamin E (page 15)
and garlic [2]. It is considered to be a trace mineral, meaning the body only
needs small amounts of it [1]. Too much selenium can call selenosis,
inducing hair loss, nausea, fatigue, and mild nerve damage [2].
Zinc (chelated)
Description:
Zinc, in its chelated form, is the
organic form of an essential trace
mineral found in food [1]. Animals
and humans absorb and digest
mineral chelates better than their
inorganic
45
Quick Facts:
Chemical properties: divalent
organic mineral
Molecular Mass: 65.38 g/mol
Metabolism:
Zinc is an essential mineral for the health of humans and animals because
many enzymes require zinc in their catalytic centre, such as alcohol
dehydrogenase [3]. In the human body, zinc interacts with a wide range of
organic ligands, serve as structural ions in transcription factors for gene
expression, and play roles in the metabolism of RNA and DNA. A notable
structural role it plays is in “zinc fingers”[3].
Dose: 0.14 mg/day | antioxidant
Effects:
Zinc is said to have antioxidant
properties, able to protect
against the accelerated aging
of the skin and muscles in the
body [3]. It was also found
ound
that zinc may delay the progression of
age-related macular degeneration and
vision loss [4]. Zinc also contributes to
the immune system by being used in
granulocytes, a type of white blood
cells that helps protect the body
against infections [2].
References: [1] Brown, T. F.; Zeringue, L. K. J Dairy Sci. 1994. 77: 181-189.
[2] National institute of Health. Office of Dietary Supplements: Zinc.
http://ods.od.nih.gov/factsheets/Zinc-QuickFacts/ (accessed Mar 26, 2012).
[3] Valko, M.; Morris, H.; Cronin, M. T. Curr Med Chem. 2005. 12: 1161-208.
[4] Age-Related Eye Disease Study Research Group. Arch Ophthalmol. 2001. 119: 1417-36.
Related Compounds:
Magnesium (page 46)
inorganic mineral form. Zinc is said to be chemically similar to magnesium
due to their common oxidation state of +2 [1]. Zinc can be found in
oysters, red meat, seafood, fortified breakfast cereals, beans, nuts, and
whole grains [2].
Magnesium
Description:
Magnesium is an alkaline metal that
acts as a cofactor to many enzymes,
including those involved in DNA
replication and maintenance [1]. The
metal is the fourth most common
46
Quick Facts:
Chemical properties: Divalent,
alkaline earth metal
Molecular Mass: 24.31 g/mol
Metabolism:
As a divalent element, Mg2+ is able to interact with ligands and enzymes as
cofactors, while competing with calcium in other metabolic pathways [3].
Many of these enzymes are DNA replication enzymes, including
telomerases [1]. The activity of these enzymes, that reduces cancer risk,
involves extending the ends of DNA strands in a Mg2+-dependent reaction.
Dose: 0.72 mg/day | anti-carcinogenic | anti-coagulant | antioxidant
Effects:
Magnesium’s diverse roles in the
cell make it an antioxidant and an
anti-tumourgenic agent [1]. Its
abilities to extend telomeres and
reduce cancer risks has also been
referred to as anti-aging effects.
Magnesium supplements have also
been used to treat heart and
kidney problems, but are also used
to treat asthma [3]. In vivo
experiments showed that
magnesium administered through
intravenous infusion increased
blood-clotting time [2]. The
reduction of platelet aggregation
was further pronounced in the
presence of acetylsalicylic acid [2].
References: [1] Rowe, W.J. Clin Interv Aging. 2012. 7: 51-54.
[2] Stanger, M.J.; Thompson, L.A.; Young, A.J.; Lieberman, H.R. Nutrition Reviews 2012: 70(2): 107-117.
[3] Swaminathan, R. Clin Biochem Rev. 2003. 24(2): 47-66.
Related Compounds:
Acetylsalicylic acid (page 39),
Potassium (page 43), Zinc (page 45)
mineral in the body, and its deficiency results in heart, kidney, and brain
problems [2,3]. Magnesium is usually consumed through green leafy
vegetables, nuts, legumes, and drinking hard water [3].
Garlic
Description:
Garlic, from the plant Allicum
sativum, is a common ingredient
used in many cultures for flavour
and its medicinal properties,
including anti-tumourgenesis, car-
dioprotection, and antithrombosis
[1,2]. Garlic can be consumed in
many ways: fresh, powdered, and
extracted in oil [1].
S-allyl cysteine, as well as ajoene and allicin, are known inhibitors of ADP-
induced platelet aggregation [2]. Ajoene, while not found directly in garlic,
can be produced from allicin. Figure 2 shows the complex relations between
many of garlic’s compounds and metabolites. Yet, despite the central role of
allicin, which is derived from S-allyl cysteine, some researchers argue that
many of garlic’s bioactive ingredients are still to be identified as non-
organosulfur compounds [3].
Effects:
The consumption of garlic is related to reduced oxidation by radicals. These
antioxidant effects include the inhibition of lipid oxidation, thus not only
reducing oxidation damage but also providing cardiovascular benefits [4].
47
Quick Facts:
Key compound: S-allyl cysteine
Properties: amino acid derivative,
hydrophobic and non-polar
Also contains: adenosine, allicin
Figure 1: S-allyl cysteine
Metabolism:
Garlic’s anti-coagulent effects is
expected to be a result of
inhibition of the platelet GPIIb-IIIa
receptor, responsible for ADP-
induced platelet aggregation [2].
Dose: 21.6 mg/day | anti-carcinogenic | anti-coagulant
Garlic’s anti-coagulant effects are
most studied, inhibiting platelet
aggregation through its
organosulfur compounds. Certain
garlic extracts also reduce
cholesterol biosynthesis [1,4].
Lastly, garlic also has
hypoglycaemic effects that may
help diabetics. Tests in mice
showed that garlic oil lowered
blood glucose levels and increased
the activity of insulin [4]. These
effects have been proposed to be
caused by allicin.
References: [1] Stanger, M.J.; Thompson, L.A.; Young, A.J.; Lieberman, H.R. Nutrition Reviews 2012. 70(2): 107-117.
[2] Rahman, K.; Billington, D. J Nutrition 2000. 130(11): 2662-2665.
[3] Amagase, H. . J Nutrition 2006. 136(3): 716S-725S.
[4] Borek, C. . J Nutrition 2001. 131(3): 1010S-1015S.
Figure 1: Image from Wikimedia Commons. Figure 2: Image cropped from [3].
Related Compounds:
Gingko biloba (page 51)
48
Figure 2: Derivatives of garlic organosulfur compounds [2].
Dose: 7.2 mg/day | anti-carcinogenic | antioxidant | anti-coagulant |
| anti-inflammatory
Ginger
Description:
Ginger, or Zingeber officinale, has
been taken for a wide range of
therapeutic effects, from nausea to
low cholesterol [1]. Ginger can be
dried, ground, or fresh, and is
often used in Asian cuisines. Much
of the research on ginger and its
bioactive components is
controversial, studies of the role of
ginger in diabetics and ovarian
cancer cells have indicated
potential health benefits [3].
6-shogaol is metabolized into several products that induce cell death. A
study using mice showed the production of several metabolites; two of
these were linked to apoptosis: 1-(4’-hydroxy-3’-methoxyphenyl)-decan-3-
ol and 1-(4’-hydroxy-3’-methoxyphenyl)-decan-3-one (or 6-paradol) [4].
49
Quick Facts:
Key compounds: 6-shogaol,
gingerols
Properties: phenolics
Also contains: sesquiterpenes,
monoterpenes [2]
Figure 1: 6-shogaol (top) and
10-gingerol (bottom)
Metabolism:
Ginger contains many phenolics
that produce anti-inflammatory
and antioxidant effects [3]. These
compounds can be inter-
converted and may also change
when cooked or heated. 6-
shogaol has been shown to induce
apoptosis in certain cancer cells,
while 10-gingerol may inhibit cell
growth, producing anti-
tumourgenic effects [3].
Effects:
In addition to its anti-tumourgenic
effects, ginger is an antioxidant
[4]. Ginger has also been shown to
have anti-inflammatory benefits
[3].
The cardioprotective role of ginger
is disputed. Ginger has been
reported to have blood-thinning
properties, though these effects
have not been confirmed in vitro
and has not been shown to
augment the affects of other
blood thinners [1]. Another study
in diabetic rats showed that ginger
reduced blood sera cholesterol by
44% [2].
References: [1] Stanger, M.J.; Thompson, L.A.; Young, A.J.; Lieberman, H.R. Nutrition Reviews 2012. 70(2): 107-117.
[2] Al-Amin, Z.M.; Thomson,M.; Al-Qattan, K.K.; Peltonen-Shalaby, R.; Ali, M. Brit J Nutr 2006. 96: 660-666.
[3] Levy, A.S.A.; Simon, O.; Shelley, J.; Gardener, M. BMC Pharmacology 2006: 6:12-19.
[4] Peng, F. et al. Fitoterapia 2012. January 10 [Epub ahead of print].
[5] Chen et al. Drug Metabolism & Disposition 2012. January 13 [Epub ahead of print].
Figure 1: Image cropped from [4]. Figure 2: Adapted from [5].
Related Compounds:
Acetylsalicylic acid (page 39)
50
Figure 2: Main metabolites of 6-shogaol [5]
6-s
ho
gao
l 1-(4’-hydroxy-3’-methoxyphenyl)-4-decen-3-ol
5-cysteinyl-1-(4’-hydroxy-3’-methoxyphenyl)-4-decen-3-ol
5-N-acetylcysteinyl-1-(4’-hydroxy-3’-methoxyphenyl)-4-decen-3-ol
5-methoxy-1-(4’-hydroxy-3’-methoxyphenyl)-decan-3-one
1-(4’-hydroxy-3’-methoxyphenyl)-decan-3-ol
5-methylthio-1-(4’-hydroxy-3’-methoxyphenyl)-decan-3-one
5-methylthio-1-(4’-hydroxy-3’-methoxyphenyl)-decan-3-ol
5-cysteinyl-[6]-shogaol
5-glutathiol-[6]-shogaol
5-cysteinylglycenyl-1-(4’-hydroxy-3’-methoxyphenyl)-4-decen-3-ol
3’,4-dihydroxylphenyl-decan-3-one
1-(4’-hydroxy-3’-methoxyphenyl)-decan-3-one apoptosis
Dose: 1.44 mg/day | neuroprotective | antioxidant | anti-coagulant
Gingko Biloba
Description:
Ginkgo Biloba is derived from a
tree, and has been used in Asian
medicines for centuries. Its
medical ingredients are found in
its leaves, and includes over forty
flavonoids (pg. 38) and terpene
trilactones, notably ginkgolides
and bilobalides [1,2]. Ginkgo
biloba seeds also contain nutrients
and compounds with potential
therapeutic benefits. The plant can
be found in tablet or powdered
form, and is commonly included in
multivitamins [1].
Many compounds result from ginkgolide metabolism, including bilobalide,
shown in Figure 2 [3]. The collective group of flavonoids and related
compounds have many antioxidant properties that involved interacting
with reactive oxygen species. Ginkgolide metabolites also interfere with
platelet formation, thus having anti-coagulant effects [1].
51
Quick Facts:
Key compounds: ginkgolides,
bilobalides
Properties: terpene trilactones
Also contains: terpenoids,
flavonoids, carotenoids
Figure 1: Common ginkgolides [2].
Metabolism:
Gingkolides are steroid
compounds that can be derived
from each other. Figure 1 shows
many common ginkgolides that
have hydroxyl groups in various
locations. The biosynthesis of
ginkgolides C is from the addition
of hydroxyl groups from simpler
ginkgolides.
Effects:
Taking ginkgo biloba and blood
thinners like warfarin and aspirin
has led to a cases of hemorrhages
[1]. Ginkgo biloba has also been
shown to interact with antiplatelet
agents, garlic, and ginseng.
Ginkgo biloba is taken for its
antioxidant and neuroprotective
properties [1]. Its extract induces
antioxidant mechanisms that
reduce oxygen radicals [3].
Consuming gingko biloba has also
been shown to improve memory
and treat Alzheimer’s, tinnitus,
dementia and schizophrenia [4].
Though no mechanism has been
elucidated, gingko’s antioxidant
role is suspected to provide its
neuroprotective benefits [3].
References: [1] Stanger, M.J.; Thompson, L.A.; Young, A.J.; Lieberman, H.R. Nutrition Reviews 2012: 70(2): 107-117.
[2] ]WHO. WHO monographs on selected medicinal plants. Geneva: World Health Organization 1999.
[3].Briskin, D.P. American Society of Plant Physiologists 2000. 124(2): 507-514.
[4] Sierpina, V.S.; Wollschlaeger, B.; Blumenthal, M. Am Fam Physician 2003. 68(5): 923-926.
Figure 1: Image cropped from [2]. Figure 2: Image cropped from [3].
Related Compounds:
Beta-carotene (page 33),
Bioflavonoids (page 35), Garlic
(page 47), Ginseng (page 57)
52
Figure 2: Bilobalide (right) is derived from ginkgolides (left).
Both are flavonoids and act as antioxidants [3].
Cod Liver Oil
Description:
Cod liver oil has been used as
medicine as early as 1789, mainly
as a treatment for rickets or
rheumatism [1]. The oil is
extracted from the fresh liver of
any fish in the genus Gadus, and
is known for its omega-3 fatty
acids, and its high Vitamin A and
D content [2]. Omega-3 fatty acids
are associated with cardiological
benefits.
the fatty acids usually incorporated in phospholipids, EPA and DHA help to
increase cell membrane fluidity and affect the structure of lipid rafts. EPA
and DHA also interact with several membrane proteins, including G-protein
coupled receptors like rhodopsin and ion channels [3].
Omega-3 fatty acids interfere with the body’s fatty acid metabolic activities,
usually competing with other fatty acids to inhibit certain pathways. For
example, EPA and DHA compete with normally abundant arachidonic acid
(AA) in the formation of thromboxanes by lipoxygenases [3]. The
anticoagulant and anti-inflammatory properties of cod liver oil are related
to the decrease in thromboxane-2 production needed for platelet
aggregation [4]. The competing pathways of thromboxane production by
omega-3 fatty acids is shown in Figure 2.
Dose: 5.04 mg/day | anti-coagulant | anti-inflammatory
53
Quick Facts:
Key compounds: Omega-3 fatty
acids [eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA)]
Properties: Hydrophobic, non-polar
Also contains: Vitamin A , Vitamin D
Figure 1: EPA and DHA
Metabolism:
Like other fatty acids, EPA and
DHA can be broken down as a
source of energy or incorporated
into the phospholipid bilayer.
Because omega-3 fatty acids
contain more double bonds than
Effects:
While usually taken for its anti-
inflammatory effects, cod liver oil
involves the intake of fatty acids
that are also be broken down as a
source of energy, leading to
potential weight gain [5].
Cod liver oil has been shown to
have some anti-coagulant effects,
though observations have been
disputed in various studies.
Frequent consumers of fish oils
have longer bleeding times,
indicating that platelet
aggregation has been inhibited [6].
These anti-coagulant effects are
significantly increased when cod
liver oil is taken with other anti-
coagulants like acetylsalicylic acid
(page 42).
References: [1] Rajakumar, K. Pediatrics 2003: 112(2):e132-135.
[2] Terkelsen, L.H.; Eskild-Jensen, A.; Kjeldsen, H.; Barker, J.H.; Hjortdal, V.E. Scand J Plast Reconstr
Hand Surg 2000: 34:15-20.
[3] Mozaffarian, D.; Wu J.H.Y. J Nutrition 2012; 142: 614S-625S.
[4] De Caterina, R.; Basta, G. European Heart Journal Supplements 2001; 3: D42-D49.
[5] Stanger, M.J.; Thompson, L.A.; Young, A.J.; Lieberman, H.R. Nutrition Reviews 2012: 70(2): 107-117.
[6] Green, M. MBJ 2011; 343:d7505.
Figure 1: Image cropped from [3]. Figure 2: Images from Wikimedia Commons, Adapted from [4].
Related Compounds:
Vitamin D (page 13), Acetyl L-
carnitine (page 23), Acetylsalicylic
acid (page 39), Alpha-lipoic acid
(page 41), Flax seed oil (page 55)
54
lipoxygenases
eicosapentaenoic
acid (EPA)
(20:5(n-4))
arachidonic
acid (AA)
(20:4(n-6))
TXA2
TXA3
Figure 2: Competing pathways for thromboxane production [6].
(series-2 thromboxanes)
inflammatory response
induces platelet aggregation
(series-3 thromboxanes)
anti-inflammatory response
inhibits platelet aggregation
Flax Seed Oil
Description:
Also known as linseed oil, the oil
from flax seed is high in omega-3
fatty acids, notably α-linolenic
acid (ALA). Flax seed, made of 35%
oil, has been shown to have
antioxidant and anti-apoptotic
effects, and has therapeutic
benefits similar to fish oils [1].
More than half of its oils are
represented by ALA by mass [2].
can increase cell membrane fluidity and affect the structure of lipid rafts.
ALA is a precursor for other omega-3 fatty acids, like eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA). Thus, flax seed oil carries
many benefits of various fatty acids that can be generated from its ALA,
including the anti-inflammatory and anti-coagulant effects of EPA and
DHA. [3].
Figure 2 shows the conversion of ALA to EPA [3,4]. The pathway involves
elongases and desaturases to lengthen the 18:3(n-3) ALA fatty acid to a
20:5(n-3) EPA fatty acid. With two more elongases, another desaturase,
and a process termed peroxisomal oxidation, the EPA fatty acid can be
converted to DHA (22:6(n-3)).
55
Quick Facts:
Key compound: α-linolenic acid
Properties: Omega-3 fatty acid,
hydrophobic and non-polar
Also contains: linoleic acid, oleic
acid, palmitic acid, stearic acid
Figure 1: α-linolenic acid (ALA)
(18:3(n-3))
Metabolism:
Flax seed oil contains many fatty
acids than can be broken down by
fatty acid oxidation or
incorporated into cell membrane
phospholipids. As an omega-3
fatty acid, ALA contains more
double bonds than most fatty and
Dose: 21.6 mg/day | anticarcinogenic | antioxidant | anti-inflammatory
| anti-coagulant
Effects:
Consumption of flax seed oil has
been linked to higher ALA levels
and increase EPA and DHA
concentrations, the main omega-3
fatty acids of cod liver oil (pg. 53).
Flax seed oil with UVC radiation
leads to a decrease in glutathione
in the skin, lens of the eyes, and
blood serum, though apoptosis
was lower with flax seed oil than
without [2]. Flax seed oil decreases
platelet aggregation and increases
bleeding time for its anti-
coagulant effects. The oil also acts
as an antioxidant by suppresses
inflammatory mediators in blood
sera and reduced oxygen radical
production [3].
References: [1] Tuluce, Y.; Oxkol, H.; Koyuncu, I. Toxicology and Industrial Health 2011. 28(2): 99-107.
[2] Prasad, K. J Cardiovasc Pharmacol. 2009. 54(5): 369-377.
[3] Barcelo-Coblign, G et al. Am J Clin Nutr. 2008. 88(3):801-989.
[4] King, M.W. “Omega-3, and -6 Polyunsaturated Fatty Acid Synthesis, Metabolism, Functions. Last
updated March 10, 2012. themedicalbiochemistrypage.org/omegafats.php (accessed March 22, 2012).
Figure 1: Image from Wikimedia Commons. Figure 2: Image adapted from [4].
Related Compounds:
Acetyl L-carnitine (page 23),
Acetylsalicylic acid (page 39),
Cod liver oil (page 53)
56
Figure 2: Conversion of ALA (found in flax seed oil) to
EPA (found in cod liver oil).
Ginseng
Description:
Radix Ginseng, or the root of the perennial herb Panax ginseng, is
commonly used in China and South Korea as a herbal remedy reported to
be anti-carcinogenic, anti-inflammatory, and antioxidant [1,2]. American
ginseng (P. guinquefolius) has also grown in popularity, and each species
has its unique effects [3]. Most studies have analyzed the effects of Asian
ginseng, usually consumed as powders, teas, tablets, or extracts, and will
be the focus of the information below.
57
Quick Facts:
Key compounds: more than 40
different triterpene saponins
(ginsenosides, panaxosides)
Properties: hydrophobic steroid
glycosides with hydrophilic R groups
Figure 1: General ginsenoside molecule (R1, R2, and R3 are variable)
G-Rg1 : R1 = -OH; R2 ,R3 = -O-Glc
Metabolism:
Shown above in Figure 1, ginsenosides and related panaxosides are
complex compounds involved in many metabolic pathways. Few specific
mechanisms have been deduced, though studies by Tawab et al. Have
studied ginsenoside breakdown in humans [4].
The most common type of ginsenoside in Panax ginseng is G-Rg1 which is
broken down into G-Rh1 and G-F1 in the digestive tract for distribution in
the body [4]. These simpler ginsenosides are further metabolized by
intestinal bacteria into many products including compound-K, which has
apoptotic properties providing ginseng with anticarcinogenic benefits [5].
This mechanism, starting with ginsenoside Rb1, is shown in Figure 2.
Dose: 86.4 mg/day | anti-carcinogenic | antioxidant | anti-inflammatory
Effects:
Ginseng has been shown to
increase blood-clotting time and
may inhibit platelet-activating
factors, while many studies
suggest that ginseng also has
roles in the immune system,
psychological functions, and may
benefit diabetics [1,2].
Ginseng has also been taken for
many therapeutic, but
unconfirmed benefits, treating
impotence, liver disease,
tuberculosis, and hypothermia.
Ginseng’s blood thinning effects
have been disputed: while some
discourage consumption with
blood-thinner warfarin, other
studies show that ginseng may not
directly interfere with warfarin and
may even inhibit its activity.
References: [1] Kiefer, D.; Pantuso, T. Am Fam Physician 2003: 68(8): 1539-1542.
[2] WHO. WHO monographs on selected medicinal plants. Geneva: World Health Organization 1999.
[3] Stanger, M.J.; Thompson, L.A.; Young, A.J.; Lieberman, H.R. Nutrition Reviews 2012: 70(2): 107-117.
[4] Tawab, M.A. et al. Drug Metabolism and Disposition 2003, 31(8): 1065-1071.
[5] Cho, S.H.; Chung, K.S.; Choi, J.H.; Kim, D.H.; Lee, K.T. BMC Cancer 2009. 9:449.
[6] Quan, L.H. Braz. J. Microbiol. 2011. 42(3): 1227-1237.
Figure 1: Adapted from [4]. Figure 2: Adapted from [6].
Related Compounds:
Gingko biloba (page 51)
58
Figure 2: Breakdown of ginsenoside Rb1 to compound K [6].
Green Tea Extract
Description:
Green tea is one of the world’s
most consumed drinks, noted for
its antioxidant properties [1]. The
drink has also been associated
with reducing cardiovascular
disease and cancer risks. Its extract
is full of bioflavonoids (pg. ___)
and contains catechins, a
compound found in many teas.
Green tea specifically contains
epigallocatechin gallate (EGCG),
which is unique to green tea [1].
The top pathway, showing the degradation of EGCG to epigallocatechin
(EGC), then to “metabolite 5” (5-(3,5-dihydroxyphenyl)-4-hydroxyvaleric
acid) was developed from a model in mice [2]. Metabolite 5 was the most
common metabolite found in the cecum and feces. The second pathway,
leading to gallic acid (3,4,5-trihydroxybenzoic acid), was seen in pigs [3].
Gallic acid and its derivatives are antioxidant, acting as a free radical
scavenger [4]. In mice, gallic acid has also been shown to have
hepatoprotective effects.
59
Quick Facts:
Key compound: catechins, including
epigallocatechin gallate (EGCG)
Properties: family of polyphenol
Also contains: flavonoids
Figure 1: Green tea’s most common
catechin: epigallocatechin gallate
Metabolism:
Green tea contains many
compounds involved in many
pathways, generating several
antioxidant compounds. Two
potential metabolic pathways for
EGCG are shown in Figure 2.
Dose: 7.2 mg/day | antioxidant | anti-coagulant
Effects:
EGCG inhibits stress-induced
apoptosis by interfering with
telomere attrition. Thus, green tea,
especially in high concentrations,
helps to reduce cell death during
times of stress [1].
Green tea catechins have been
recognized for its benefits outside
of antioxidant properties,
including the reduction of blood
cholesterol and sugar levels [2].
The consumption of green tea has
also been related to reducing
cardiovascular disease and breast,
prostate, colorectal, and lung
cancers [1].
References: [1] Bandele, D.J.; Osheroff, N. Chem Res Toxicol. 2008. 21(4): 936-943.
[2] Takagaki, A.; Nanjo, F. J. Agric. Food Chem. 2010. 58(2): 1313-1321.
[3] van’t Slot, G.; Humpf, H.U. J. Agric. Food Chem. 2009. 57(17): 8041-8048.
[4] Rasool, M.K. J Pharm Pharmacol. 2010. 62(5): 638-643.
Figure 1: Image from Wikimedia Commons [3]. Figure 2:Adapted from [2,3].
Related Compounds:
Vitamin B1 (page 3), Bioflavonoids
(page 35), Rutin (page 37)
60
Figure 2: Potential pathways for EGCG metabolism.
(metabolite 5: 5-(3,5-dihydroxyphenyl)-4-hydroxyvaleric acid.)
EGCG
EGC
gallic acid
metabolite 5
How Compounds Interact
While each of the 31 compounds have their unique roles in the anti-
aging supplement, together they interact with networks of
metabolic pathways to produce their intended effect. The diagram
on page 64 shows many of these connections compiled from the
individual interactions noted from pages 3-60, including synergistic
properties, compounds that form complexes, and the direct
conversion of some ingredients to others.
61
Ingredient Inter-conversion and Overlap
Firstly, the nature of these ingredients result in many direct
connections. For example, rutin and several compounds in gingko
biloba belong to the group of bioflavonoids. These connections are
indicated by the blue arrows, with a compound pointing towards the
compounds with the broader group. As many extracts contain many
compounds that represent other ingredients, such overlap is very
common and increases the actual dose of these ingredients. An
example is green tea extract, which contains Vitamin B1, rutin, and
bioflavonoids.
Inter-conversion between compounds is also very common. Similar
ingredients like cod liver and flax seed oils also contain omega-3
fatty acids that are in the same metabolic pathways. Other
compounds, like N-acetyl cysteine, is a direct precursor to L-
glutathione.
Synergistic Partnerships
Many compounds are able to further the effects of other
compounds, such as Vitamin C’s ability to increase the antioxidant
properties of Vitamin E. The result is a combined effect greater than
the sum of the effects of the individual compounds, not surprising
as many of these compounds have similar properties. Synergy may
be due to a compound increasing the absorption of another
compound, or interacting with a pathway to significantly push a
reaction forward.
Synergistic interactions are shown with double-headed green
arrows. As shown on page 64, many of the vitamins interact
synergistically, notably the B-vitamins. The presence of folic acid is
usually critical to the absorption of the other B-vitamin, while the B-
vitamins acts as a cofactor to folic acid, making the presence of
multiple B-vitamins necessary for their respective benefits.
Many of the extracts work together to produce an anti-inflammatory
effect, notably ginseng, gingko biloba, and garlic. Ginger’s anti-
coagulant effects are extended when taken with acetylsalicylic acid.
Other synergistic partnerships include acetyl L-carnitine and α-lipoic
acid, and magnesium and acetylsalicylic acid.
Increased Metabolic and Catabolic Activity
Similar to synergistic partnerships, some compounds increase the
efficacy of other compounds by assisting in their breakdown. Yet,
these interactions are not synergistic because they are a one way
relationship. For instance, Vitamin E is necessary for cleavage of β-
carotene to Vitamin A, though β-carotene does not increase the
efficacy of Vitamin E.
Acetyl L-carnitine an acetylsalicylic acid increases the breakdown of
fatty acids, including those found in cod liver and flax seed oils.
These are shown by the red-dashed lines.
Complexes
A complex can be formed between Chromium and Vitamin B3. This
type of interaction is similar to a synergistic one, because the
presence of each component is important to its beneficial effects,
but in this case, both compounds act together to achieve its anti-
aging properties. Chromium also complexes with picolinate, an
artificial derivative of Vitamin B3. This interaction is shown with a
gray dotted line.
62
Inhibitors
Inhibitory interactions are shown with a yellow line, with the diamond
towards the inhibited compound. For example, the presence of ASA
inhibits the activity of vitamin C, specifically by blocking its
absorption, while potassium inhibits vitamin B12 absorption. While
this interaction is explicit, inhibitory actions are likely to be found
among many of the compounds involved in similar pathways. Because
main structures are similar, compounds may compete for the same
enzymes and decrease the activity of each individual ingredient.
Helps to Absorb or Regenerate
Some compounds, like Coenzyme Q, are necessary for the absorption
of another ingredient, like vitamin E. Like the “increased metabolic
activity” arrows, these purple arrows indicate one way interactions. In
contrast to catabolism, these compounds amplify the effect of
another compound by aiding in its absorption of by regenerating
spent metabolites. Regeneration of other compounds also
significantly increase their beneficial effects, and may also be a one-
way effect. An example of this type of relationship is the regeneration
of vitamin C by alpha-lipoic acid.
Complex Interactions
Lastly, given 31 compounds with varying individual effects yet similar
metabolic pathways, various interactions occurring between two
compounds are also possible. There are two examples: cod liver oil
and acetylsalicylic acid both work together to achieve anti-coagulant
properties, yet ASA also assists in the breakdown of cod liver oil
among other fats. The chromium from chromium picolinate forms a
complex with vitamin B3, while picolinate can be converted to itamin
B3.
The complexities of these interactions indicate that the DSP may work
in many different ways. The interaction diagram will only get busier as
more metabolic pathways are elucidated, and more effects confirmed.
63
Interaction Diagram
Vit
am
in B
1
Legend
Is a type of / converts to...
Acts synergistically with...
Helps to break down...
Complexes with ...
Inhibits...
64 Helps to regenerate/
synthesize/absorb ...
Conclusion
65
The complex dietary supplement provides a promising
future for the treatment and prevention of age-related declines.
This booklet helps to understand some of the complex interplay
that exists between the metabolic pathways of each compound
that may have contributed to the supplement’s overall combined
anti-aging properties. As research continues on each of the
individual compounds, more links can be drawn further
understand how the anti-aging supplement achieves its benefits.
The next step is to determine whether reduced amounts of
ingredients in the DSP will achieve similar effects and to identify
the most optimal number and type of ingredients that should be
included.
References
The following references were used in the introduction. All compound-
specific references are included in the footnotes from page 3 to 60, while
the interaction pages are a summary of the interactions noted on the
compound-specific pages. Reference [6] outlines the DSP.
[1] Chen, P., Ratcliff, G., Belle, S. H., Cauley, J. A., DeKosky, S. T. and Ganguli, M.
Patterns of cognitive decline in presymptomatic Alzheimer disease. Arch Gen
Psychiatry. 2001. 58:853–858
[2] Miquel. J., Economos. A. C., Fleming. J. and Johnson. J. E. Mitochondrial role in
cell aging Exp Gerontol. 1980. 15:575–591.
[3] Beckman, K. B. and Ames, B. N. The Free Radical Theory of Aging Matures.
Physiol Rev. 1998. 78:547–581.
[4] Aruoma, O. I., and Butler, J.. et al. The antioxidant action of N-acetylcysteine: its
reaction with hydrogen peroxide, hydroxyl radical, superoxide, and
hypochlorous acid. Free Radical Biology & Medicine. 1989. 6, 595-597
[5] Fang, Y. Z., Yang, S. & Wu, G. Free radicals, antioxidants, and nutrition. Nutrition,
2002,18, 872-879
[6] Lemon, J. A., Boreham, D. R. and Rollo, C. D. A dietary supplement abolishes age-
related cognitive decline in transgenic mice expressing elevated free radical
processes. Exp Biol Med. 2003, 228, 7, 800-810.
[7] Aksenov, V., Long, J., Lokuge, S., Foster, J. A., Liu, J. and Rollo, C. D. Dietary
amelioration of locomotor neurotransmitter and mitohondrial aging. Exp Biol
Med. 2010, 235, 1, 66-76.
[8] Aksenov, V., Long, J., Liu, J, Szechtman, H., Khanna, P., Matravadia, S. and Rollo,
C. D. A complex dietary supplement augments spatial learning, brain mass, and
mitochondrial electron transport chain activity in aging mice. AGE. 2011. 10.
1007
66
Vitami
L-glutathione
vitamin B1
vitamin B
vitamin B12 vitamin C
vitamin B1 vitamin D vitamin E
folic acid
L-glutathione
chromium picolinate
coenzyme Q10
DHEA
Melatonin bioflavonoids
Rutin Acetylsaliclyic acid
α-lipoic acid
β-carotene
potassium
selenium zinc
magnesium
garlic
ginger
Gingko biloba cod liver oil flaxseed oil ginseng reen tea extract
coenzyme Q10
Gingko biloba
Melatonin
vitamin B1
vitamin B6
vitamin B12 vitamin C
vitamin B1 vitamin D vitamin E
folic acid
L-glutathione
chromium picolinate
Coenzyme
DHEA
Melatonin
bioflavono
Rutin Acetylsaliclyic acid
α-lipoic acid
β-carotene
potassium selenium zinc
magnesium
garlic
ginger
cod liver oil
flaxseed oil
green tea extract
coenzyme Q10 bioflavonoids
vitamin B1
vitamin B6 vitamin B3
vitamin B12 vitamin C
vitamin B1 vitamin D vitamin E
folic acid
n-acetyl cysteine L-glutathione
chromium picolinate
coenzyme Q10
DHEA
Melatonin
bioflavonoids
Rutin Acetylsaliclyic acid
α-lipoic acid
β-carotene
potassium
selenium zinc
magnesium
garlic
ginger
Gingko biloba cod liver oil flaxseed oil ginseng reen tea extract
coenzyme Q10
Gingko biloba
bioflavonoids
Melatonin
vitamin B1
vitamin B12 Vita
vitamin D vitamin E
folic acid L-glutathione
coenzyme Q10
DHEA
Me
bioflavonoids
Rutin Acetylsaliclyic acid
ic acid β-ca
otassium magne
garlic ginger
Gingko biloba cod liver oil flaxseed oil ginseng
coenzyme Q10
Gingko biloba
bioflavonoids
Melatonin L-glutathione
Melatonin
Acetylsaliclyic acid
β
β
Acetylsaliclyic acid
β-carotene DHEA
ginseng Mela
Flaxseed
selenium
magnesium
green tea extract
coenzyme Q10 flaxseed oil
Acetylsaliclyic acid
bioflavonoids DHEA Gingko biloba