T3

Fuel
Supports metabolism
tm

at the cellular level.

Allows you to break
fat loss plateaus.
Supports and fuels
healthy thyroid
function.
 2

T3
A thyroid hormone that affects every cell in your body

The thyroid gland secretes hormones that are systemically involved in many
cellular processes and vital to a properly functioning metabolism. Many peo-
ple suffer from inadequate production of thyroid-derived hormones, which
results in a laundry list of adverse effects:

Fatigue, dry and coarse skin, feeling cold, cool extremities, poor memory and con-
centration, constipation, hair loss, weight gain with poor appetite, slow pulse rate,
shortness of breath, swelling of the limbs, hoarse voice, delayed relaxation of ten-
don reflexes, carpal tunnel syndrome, abnormal sensation, pleural effusion, asci-
tes, pericardial effusion, poor hearing, feelings of tiredness, poor ability to tolerate
cold, and weight gain (Premawardhana et al., 2008).

A dysfunctional thyroid gland is often overlooked in medicinal practice, but it

can be the underlying cause of many symptoms. The thyroid gland is a butter-
fly-shaped organ located just below the Adams apple in the neck. Composed
of small sacs, this gland is filled with an iodine-rich protein called thyroglobulin
along with the thyroid hormones thyroxine (T4) and triiodothyronine (T3).

The primary function of these two hormones is to regulate the metabolism by

controlling the rate at which the body converts oxygen and nutrients into en-
ergy. In fact, the metabolic rate of every cell in the body is regulated by thyroid
hormones, primarily T3 (Videla et al., 2006).

T3 Fuel
 3

Why is this important?

Thyroid hormones are required for the normal functioning of numerous tis-
sues in our body. Principally, the thyroid gland secretes thyroxine (T4), which
is converted into the active form triiodothyronine (T3). Conversion from T4 to
T3 occurs through the action of a very important enzyme called iodothyronine
deiodinase, which requires the mineral selenium (Maia et al., 2011).

T3 is extremely important; in fact, it actually binds to a hormone receptor in

the nucleus of cells, activates genes, and directly stimulates the production of
specific proteins. Interestingly enough, almost all of the thyroid hormones in
circulation are bound to plasma proteins only a free and unbound thyroid
hormone is biologically active (Garber et al., 2012). More specifically, 99% of
circulating thyroid hormones are bound to carrier proteins, rendering them
metabolically inactive (Nussey et al., 2001). To produce thyroid hormones, the
thyroid gland requires certain levels of iodine and tyrosine, an amino acid that
is controlled by the thyroid-stimulating hormone (TSH). If there are insuffi-
cient levels of iodine, selenium, tyrosine, or thyroid-stimulating hormone, the
entire process is compromised and the amount of thyroid hormone decreases
(Fatourechi, 2009).

The hypothalamicpituitarythyroid axis plays a key role in keeping thyroid

hormone levels within normal limits. Production of thyroid-stimulating hor-
mone by the anterior pituitary gland is stimulated by thyrotropin-releasing
hormone (TRH), which is released from the hypothalamus. The production of
thyroid-stimulating hormone and thyrotropin-releasing hormone is reduced
by thyroxine through a negative feedback process. Not having enough TRH,
which is uncommon, can lead to not having enough TSH and therefore an in-
adequate level of thyroid hormone production (Fatourechi et al., 2009). The
thyroid gland controls how quickly the body uses energy, makes proteins, and
controls how sensitive the body is to other hormones. In terms of energy, we
can look down to the most basic cellular level to truly grasp the importance of
thyroid hormones effects on energy metabolism and ATP.

T3 Fuel
 4

ATP is the Human Energy Currency

Adenosine triphosphate is one of the most basic energy-releasing compounds

in your body. You can basically think of it as the energy currency for all cells.
ATP supports energy-consuming reactions, such as muscle contractions, so-
dium/potassium pumping, and calcium/sodium pumping, all of which are es-
sential in a normal heart function. To put it bluntly, you would die without ATP.

ATP is created in large quantities in the mitochondria of cells. Mitochondria

are like little powerhouses and use oxygen in a process known as oxidative
phosphorylation to produce ATP. ATP synthesis requires the presence of thy-
roid hormones, which activate oxidative phosphorylation. When your thyroid
status is insufficient, mitochondrial oxidation decreases, leading to ATP deple-
tion, which cannot be compensated for by other mechanisms like glycolysis
(Popovici et al., 1979). Glycolysis occurs under conditions of little to no oxy-
gen and glycolysis impairs membrane permeability and mitochondrial func-
tion, causing an enzyme release and pump failure. Furthermore, when thyroid
hormones are reduced, the activity of ATP-ase, an enzyme involved in trans-
forming chemical energy into mechanical energy, is severely depressed.

Conversely, when the thyroid gland over-secretes thyroid hormones, a condi-

tion called hyperthyroidism, an ATP deficiency occurs due to the uncoupling of
oxidative phosphorylation. What actually ends up happening is a state of met-
abolic inefficiency where there is a disproportion between the consumption
of oxygen and nutrients and actual ATP production. The excess hormones T4
and T3 cause trace metal (magnesium, copper, zinc, iron, etc.) binding, which
inhibits the enzyme activity linked to ATP synthesis (Popovici et al., 1979).

ATP formation is directly tied to the health of the mitochondria. Without a

properly functioning thyroid gland and hormone output, this entire process is
compromised.

T3 Fuel
 5

We all want mitochondrial health and efficiency

What happens when there is a loss of function in the mitochondria? This key
cellular component responsible for energy production can result in excess fa-
tigue if it is not functioning properly. On a molecular level, a reduction in mi-
tochondrial function can occur as a result of the following changes:

1. A loss of maintenance of the electrical and chemical transmembrane po-

tential of the inner mitochondrial membrane;

2. Alterations in the function of the electron transport chain;

3. A reduction in the transportation of critical metabolites into mitochondria

(Nicolson, 2013).

The result is a reduction in ATP, which causes signs of aging, and essentially all
chronic diseases, including Alzheimers disease, Parkinsons disease, Hunting-
tons disease, amyotrophic lateral sclerosis, Friedreichs ataxia, atherosclerosis,
and other heart and vascular conditions, diabetes and metabolic syndrome,
multiple sclerosis, systemic lupus erythematosus, autism spectrum disorders,
schizophrenia, bipolar disorders, gastrointestinal disorders, chronic fatigue
syndrome, fibromyalgia, cancer, and chronic infections (Nicolson, 2013).

Mitochondrial dysfunction arises from an inadequate number of mitochon-

dria, an inability to provide the necessary substrates to mitochondria, or a dys-
function in their electron transport and ATP synthesis machinery. As a result
of aging and chronic diseases, oxidative damage to mitochondrial membranes
impairs mitochondrial function (Piper et al., 1987; Logan et al., 2001).

T3 Fuel
 6

Why does this information matter?

1. A properly functioning thyroid is vital to your health and well-being, and is

also involved in most bodily functions.

2. Due to its complexity, regulatory roles and rate-limiting compounds, one or

two ingredients arent going to cut it.

3. A complex hormone requires multiple, properly dosed and optimal ingredi-

ents to get the best and safest results!

4. T3 Fuel is a revolutionary and targeted supplement designed to optimize

the thyroid processes and prioritize active thyroid hormone.

Tying It All Together:

A Formulation Based on Science and Results:

Iodine: 100mcg

Iodines major role in the body is to make thyroid hormone. Iodine ac-
counts for 65% of the molecular weight of T4 and 59% of T3, making this
mineral extremely important in thyroid health (Patrick, 2008). Iodine is an
essential mineral in the human body due to its role in cognition, develop-
ment and metabolism. Thyroid hormones are also made from the amino
acid tyrosine, and are stored in iodine-containing proteins called thyro-
globulin. Even the nomenclature reiterates iodines importance, as T4
and T3 have 4 and 3 atoms of iodine per molecule, respectively.

Our diet and salt products already contain iodine. Isnt that enough?

Supplementation of 100-300g iodine in a population of healthy subjects

without iodine deficiency for six months was found to cause minor anti-
inflammatory effects, which were measured by a reduction in inflamma-
tory markers, IL-6 and C-reactive protein (Soriguer et al., 2011). Further-

T3 Fuel
 7

more, micronutrients like iodine and selenium are required for thyroid
hormone synthesis and function. Iodine is an essential component of thy-
roid hormones and its deficiency is considered the most common cause
of preventable brain damage in the world. Currently, 800 million people
are affected by iodine deficiency disorders, which include goiter, hypo-
thyroidism, mental retardation, and a wide spectrum of other growth and
developmental abnormalities (Triggiani et al., 2009). Iodine supplementa-
tion has resulted in dramatic improvements in many areas, but iodine de-
ficiency is not only for a problem for developing countries. In fact, certain
subpopulations, such as vegetarians, may not achieve an adequate io-
dine intake, even in countries considered iodine-sufficient (Triggiani et al.,
2009). Furthermore, iodine intake is declining in many countries, where
their lack of monitoring of iodine nutrition can lead to a reappearance of
goiter and other iodine deficiency disorders.

Selenium: 300mcg

Iodine has a nutritional relationship with another important mineral called

selenium. A family of enzymes dependent on selenium, called deiodin-
ases, actually converts T4 to T3 (the active hormone) by removing an
iodine atom from the tyrosine component. These enzymes also convert
T4 to reverse T3 (rT3) by removing an inner ring iodine atom. Reverse T3
does not cause thyroid hormone activity and actually blocks the thyroid
hormone receptors in the cell, thereby hindering the action of regular T3
(Khrle, 1995). Three different selenium-dependent iodothyronine deio-
dinases (Types I, II, and III) can both activate and deactivate thyroid hor-
mones, making selenium an essential micronutrient for normal develop-
ment, growth, and metabolism (Triggiani et al., 2009).

Selenium also plays a role in protecting the thyroid gland itself.

The cells of the thyroid generate hydrogen peroxide, an oxidant, and use
it to make thyroid hormone. Selenium protects the thyroid gland from
the oxidative damage caused by these reactions. Selenium is found in
the form of selenocysteine in the center of enzymes that protect the thy-
roid gland from free radicals damage. In this way, selenium deficiency can
exacerbate the effects of iodine deficiency. Substances introduced with

T3 Fuel
 8

food, such as thiocyanate and isoflavones or certain herbal preparations,

can also interfere with micronutrients and influence thyroid function.
Many health-conscious consumers are now adding new supplements or
healthy foods to their diet, but they may be inadvertently decreasing the
amount of many minerals needed for proper thyroid function. This may
interfere with a class of enzymes and transporters called selenoproteins
(proteins with selenium in them), many of which are antioxidant enzymes.
In these selenoproteins, selenium acts as the active site where molecules
can bind (Papp et al., 2007).

Another interesting and useful function of selenium is its potential to aid

glucose metabolism by acting as an insulin mimetic or mimicker (Stapleton,
2000), thus aiding the deposition of glucose into both fat and muscle cells
(Frnsinn et al., 1996). Therefore, the consequences of having low levels of
selenium can have a significant impact on overall metabolic function.

Zinc: 15mg

Zincs importance can be demonstrated easily by examining its role as a

cofactor in over 300 enzymes involved in gene expression, cell prolifera-
tion, and signal transduction (Prasad, 1994). If the body is deficient in
zinc, the activity of these enzymes will be compromised. Unfortunately,
there is a wide occurrence of zinc deficiency, resulting in major impacts
on multiple aspects of human health (Haase et al., 2007). We will fo-
cus on zincs role in regulating thyroid function and the immune system
(Prasad, 2008).

Zinc may be helpful for people with low T3 levels and may contribute to
the conversion of T4 to T3. In several studies, zinc deficiency lowered T3
and free T4 concentrations by approximately 30% (Kralik et al., 1996).
Furthermore, in a group of patients with low levels of free T3 and normal
T4, but elevated reverse T3 and mild to moderate zinc deficiency, taking
supplemental zinc for 1 year normalized their total T3 levels, decreased
the rT3 levels, and normalized TSH levels (Nishiyama et al., 1994). Finally,
in a study of female college students, zinc supplementation was found to
increase thyroid hormone production and notable T3 levels (Maxwell et
al., 2007). Zinc supplementation appeared to have a favorable effect on

T3 Fuel
 9

thyroid hormone levels, particularly total T3, as well as resting metabolic

rate (Maxwell et al., 2007).

Zinc is required for the synthesis of thyroid hormones, the deficiency of

which can result in hypothyroidism. Conversely, thyroid hormones are
essential for the absorption of zinc, so hypothyroidism can result in ac-
quired zinc deficiency (Betsy et al., 2013). However, as always, too much
of a good thing can be dangerous. Like iodine, too much zinc may sup-
press thyroid function by interfering with copper absorption (Taneja et
al., 2008). Therefore, the dose in T3 is specifically formulated to elevate
thyroid status without interfering with other mineral levels.

Zinc's main role in the body is as a component of several enzymes called

metalloproteins. One that is of particular interest is called the superoxide
dismutase enzyme; an endogenous antioxidant that utilizes both zinc and
copper (Abreu et al., 2010). It protects against the oxidant superoxide in
nearly all cells and reduces oxidative stress. Zinc has been reported to act
via the insulin receptor and phosphorylate Akt in vitro, which is down-
stream of the insulin receptor (Jansen et al., 2012). Zinc can also increase
the uptake of glucose into cells that express insulin-sensitive GLUT4 (Il-
ouz et al., 2002).

Citrullus Vulgaris Peel Extract: 400 mg

Citrullus vulgaris peel extract has certain fascinating properties that en-
able the stimulation of T4 synthesis at the glandular level (the only source
for T4 synthesis) and facilitate the conversion of T4 to T3 (Laurberg, 1984).
In a preliminary study, Citrullus vulgaris was evaluated using standardized
doses; in the 10-day period, a significant decrease in liver, heart and kid-
ney lipid peroxidation with a concomitant increase in serum levels of both
the thyroid hormones T3 and T4 was noted (Parmar et al., 2009). Further-
more, in a second experiment, a thyroid function inhibitor was adminis-
tered for 10 days to decrease the serum concentration of both the thyroid
hormones (T3 and T4). However, simultaneous administration of the in-
hibitor and Citrullus vulgaris peel extract at doses used in Experiment 1
restored the level of both the thyroid hormones (Parmar et al., 2009).

T3 Fuel
 10

L-tyrosine: 250mg

L-tyrosine is vital to thyroid health because of its use by cells in the colloid
of the thyroid gland to help form the thyroid hormones triiodothyronine
(T3) and thyroxine (T4). The thyroid gland uses both the amino acid L-ty-
rosine and iodine as major constituents of the thyroid hormones. L-tyro-
sine is a naturally occurring amino acid produced to stimulate thyroxine,
the hormone produced by the thyroid gland. The body needs L-tyrosine
for many functions and it is especially important in thyroid performance.
In short, a lack of L-tyrosine in the diet can create hypothyroid conditions.

Magnesium: 100mg

Magnesium is an essential dietary mineral and the second most preva-

lent electrolyte in the human body. Every single organ in your body uses
magnesium, but it is particularly important for the kidneys, muscles and
heart. It is also used as a treatment for an under-active thyroid caused by
magnesium deficiency.

Unexpectedly, magnesium deficiencies are common in developed coun-

tries and can result in increased blood pressure, a reduction of glucose
tolerance, and neural excitation. The reason that these deficiencies are
so prevalent in a western diet is because many common food choices are
poor sources of magnesium.

In supplemental form, when used to treat a deficiency, magnesium acts

as a sedative, reducing blood pressure and improving insulin sensitivity.
Magnesium is used in the body primarily as an electrolyte and a mineral
cofactor for enzymes. As an electrolyte, it serves to maintain fluid bal-
ance, and as a cofactor, it has a role in over 300 enzyme systems, most
notably ATP and Adenyl Cyclase. It is also required for the activation of
creatine kinase as well as many of the enzymes in the energy pathway
(Garfinkel et al., 1984).

T3 Fuel
 11

L-carnitine: 200mg

L-carnitine is a naturally occurring amino acid which transports fatty acids

into the mitochondria for fat breakdown in a process known as -oxidation
(Marcovina et al., 2013). L-carnitine deficiency is associated with reduced
mitochondrial function, insulin resistance, and coronary artery disease
(Nicolson, 2013). Unfortunately, L-carnitine is usually maintained within
relatively narrow concentration limits; thus, dietary supplementation is
important to maintain optimal L-carnitine concentrations within cells (Re-
uter et al., 2012). L-carnitine supplementation has been successfully used
in clinical disorders characterized by low concentrations of L-carnitine or
impaired fatty acid oxidation, such as diabetes, sepsis, renal disease, and
cardiomyopathy (Marcovina et al., 2013).

Why is L-carnitine in this formulation?

Interestingly enough, L-carnitine is a peripheral antagonist of thyroid

hormone action, meaning that it inhibits both triiodothyronine (T3) and
thyroxine (T4) entry into the cell nuclei. L-carnitine helps reverse hyper-
thyroid symptoms (and biochemical changes in the hyperthyroidal direc-
tion) as well as minimizing hyperthyroid symptoms. A very recent clinical
observation proved the usefulness of L-carnitine in the most serious form
of hyperthyroidism, which is aptly called thyroid storm. Since hyperthy-
roidism significantly decreases the tissue deposits of carnitine, there is a
very good reason for using L-carnitine in this formulation (Benvenga et
al., 2004).

In a randomized, double-blind, placebo-controlled 6-month trial, L-car-

nitine was reported to both reverse and prevent nine hyperthyroidism-
related symptoms (Benvenga et al., 2001). L-carnitine was also found to
be effective and beneficial for increasing bone mineralization. Because
hyperthyroidism depletes the bodys deposits of carnitine and since car-
nitine has no toxicity, nor contraindications or negative interactions with
drugs, carnitine is deemed safe for use. In fact, supplementation with
L-carnitine appears to be quite safe with doses up to 2 grams per day
(Nicolson, 2013). It has even been used on centenarians in a randomized
clinical control trial for 6 months. These participants were generally found

T3 Fuel
 12

to have muscle weakness, decreased mental health, impaired mobility,

and poor endurance. By the end of the study, the treated group showed
significant improvements in physical fatigue, mental fatigue, and fatigue
severity. They also showed reductions in total fat mass, increased muscle
mass, and an increased capacity for physical and cognitive activity due to
the reduction of fatigue and improved cognitive function (Malaguarnera
et al., 2007).

Resveratrol: 250mg

When we grow older, cellular activity and mitochondrial function gener-

ally decline. Resveratrol is a naturally occurring polyphenol with wide-
ranging health benefits, including well-researched effects related to pro-
moting mitochondrial biogenesis during the aging process (Ungvari et al.,
2011).

Resveratrol activates two very important proteins, SIRT1 and PGC1-.

Akieda-Asai et al. (2010) reported that SIRT1 is highly present in the an-
terior pituitary, which produces thyroid stimulating hormone (TSH) and
regulates thyroid hormone secretion. This indicates that the control of
TSH release is strongly regulated by SIRT1 and is therefore important for
regulating thyroid hormone release.

Evidence has highlighted deacetylase sirtuin 1 (SIRT1) as a critical factor for

the regulation of mitochondrial function. SIRT1 and PGC1- are now recog-
nized as being directly involved in the control of mitochondrial biogenesis and
metabolism (Aquilano et al., 2010). PGC1- is seen as a master regulator for
the working parts of the mitochondria (Scarpulla, 2008). PGC1- is also able to
strongly interact with and co-activate the nuclear respiratory factor 1 (NRF-1)
(Puigserver et al., 2003). Furthermore, NRF-1 is implicated in interactions with
several mitochondrial genes, including the mitochondrial transcription factor A
(TFAM), one of the most important mammalian transcription factors for mito-
chondrial DNA (mtDNA) (Kaufman et al., 2007). Therefore, PGC1- forms an
energy-sensing cellular base that controls mitochondrial function and provides
a link between mitochondria and the effects of the aging process.

T3 Fuel
 13

Recently, a study investigating the effects of resveratrol on mitochondrial

biogenesis (Davinelli et al., 2013) found that it caused a significant increase
in mitochondrial mass and an increase in SIRT1 enzymatic activity, thereby
stimulating mitochondrial biogenesis. Resveratrol is being used extensively in
obesity research, as it has been shown to have body fat lowering properties
in animals and humans (Ahn et al., 2008; Baile et al., 2011; Baur et al., 2006;
Timmers et al., 2011). These mechanisms include inhibiting fat cells from being
created, increasing the rate of fat cell death, and stimulating the release of fat
from cells. Whats even more interesting about resveratrol is its involvement
in thermogenesis in fat and muscle tissue. Thermogenesis is heat production
created by uncoupling proteins in the mitochondria that uncouple oxidative
phosphorylation. Therefore, instead of producing cellular energy, they pro-
duce wasteful heat, which cannot be harnessed by the cell.

When a group of rats were fed an obesogenic diet with resveratrol in a dose of
30mg/kg body per day for 6 weeks, researchers found that resveratrol caused
a significant increase in SIRT1 expression and in PGC-1, which induces mi-
tochondrial biogenesis (Alberdi et al., 2013). The uncoupling of Protein 1 was
significantly increased, which may be the result of increased levels of PGC-
1. Furthermore, resveratrol caused a strong increase in mitochondria and
uncoupling protein in muscle. The results indicate that resveratrol increases
uncoupling protein expression in adipose tissue and muscle and contributes
to energy dissipation throughout the body. This leads to increased energy ex-
penditure and an actual reduction in energetic efficiency.

The effects of resveratrol in improving cellular function and overall health

seem to directly or indirectly depend on the activation of SIRT1 ((Danz et al.,
2009). Furthermore, resveratrol has been known to have antioxidative prop-
erties due to its scavenging of free radicals (Leonard et al., 2003). In a recent
investigation, resveratrol was found to inhibit liver X receptor- (LXR), a reg-
ulator of de novo fatty acid synthesis which can stimulate fatty liver disease
(Jin et al., 2013).

It has been known for nearly a century that calorie restriction causes health-
improving effects. Reducing calorie intake to 2040% below your normal in-
take without compromising your nutrient needs preserves metabolic health
and promotes longevity. This is great news, but lets be realistic

T3 Fuel
 14

Long-term fasting or massively restricting food intake is not a feasible option for
long periods of time.

Resveratrol causes the expression of various genes that mimic caloric restric-
tion, which appears as the most universal life-extending manipulation (Liu et
al., 2013). As noted, resveratrol is the direct activator of SIRT1, a NAD+-de-
pendent protein deacetylase, and regulates various metabolic pathways (Lak-
shminarasimhan et al., 2013).

The question is: how does this happen on a cellular level?

SIRT1 binds to a component of the nuclear lamina and nuclear matrix (called la-
min A), a skeleton that basically forms the nucleus of a cell. The binding of lamin
A to the SIRT1 protein is critical for SIRT1 activation. It is thought that resvera-
trol activates SIRT1 through the binding of lamin A with SIRT1 (Ghosh, 2013).

A major regulator of liver gluconeogenesis is thyroid hormone, which acts

through its nuclear receptor to express the genes phosphoenolpyruvate car-
boxykinase (PCK1) and glucose-6-phosphatase (G6PC). The forkhead tran-
scription factor FOXO1 is also an important regulator of these genes.

SIRT1 actually deacetylates FOXO1, which can then cause the transcriptional
activation of PCK1 and G6PC, as was found recently in a study investigating
human and mouse liver cells (Singh et al., 2013). Their results show that thy-
roid hormone-dependent deacetylation of a second metabolically regulated
transcription factor represents a novel mechanism for transcriptional integra-
tion with cellular energy status.

Growing evidence has indicated that SIRT1, one of a number of proteins in-
duced by calorie restriction, serves as a key molecule in the regulation of mi-
tochondrial biogenesis, energy homeostasis, and insulin sensitivity. In 2003,
resveratrol was discovered to be a potent small-molecule activator of SIRT1
(Timmers et al., 2013). In a study by Timmers et al. (2011), resveratrol was
administered at 150 mg/day for 30 days and clearly had health effects that
mimicked the effects of calorie restriction. Resveratrol reduced sleeping and
resting metabolic rate without body weight changes. Skeletal muscle mito-
chondrial function and fat oxidative capacity improved. Furthermore, fasting
plasma glucose and insulin values were slightly decreased by resveratrol.

T3 Fuel
 15

We have demonstrated that resveratrol also exhibits very strong anti-

inflammatory effects in human adipose tissue. This observation could be
of great clinical importance, as the low-grade inflammation associated
with obesity may be the underlying mechanism coupling obesity and its
metabolic consequences.

Is it safe?

In terms of human safety and pharmacokinetic properties, the available

data is fairly solid; neither short-term exposure to high doses of resvera-
trol (5 g daily for 28 days) nor long-term exposure to lower doses (8 mg
daily for one year) has shown any adverse effects (Poulsen et al., 2013).

T3 Fuel:
The supplement for a properly functioning metabolism
T3 Fuel combines some of the most vital and fundamental ingredients that
will have your thyroid gland operating at optimal efficiency. The addition of
the two largest components of thyroid hormones, iodine and tyrosine, ensures
that you have the raw materials necessary to construct these powerful hor-
mones. Furthermore, selenium is added in the proper dose to ensure conver-
sion of the inactive form of thyroid hormone, T4, into the active form T3. To
avoid the common deficiency of zinc, 15mg is added to avoid hypothyroidism.
Using the unique ingredient Citrullus vulgaris peel extract, levels of T4 and T3
can be significantly elevated. Additionally, a proper dose of magnesium is used
to prevent an under-active thyroid gland and to enhance metabolic function-
ing. While most components in T3 Fuel are used to prevent hypothyroidism,
the addition of L-carnitine is used to prevent hyperthyroidism from occurring,
also helping to avoid muscle weakness, decreased mental health, impaired
mobility, and poor endurance. Finally, resveratrol is used in a robust dose to
cause the activation of SIRT1. SIRT1 promotes the secretion of thyroid stimu-
lating hormone (TSH) and regulates thyroid hormone secretion. Furthermore,
it imparts all the metabolic positives of calorie restriction without actually re-
stricting calories. Unlike any other thyroid supplement, T3 Fuel uses properly
dosed, effective and well-researched ingredients designed for optimal results.

Get your supply at www.T3Fuel.com

T3 Fuel
 16

References
Ahn, J., Cho, I., Kim, S., Kwon, D., & Ha, T. (2008). Dietary resveratrol alters lipid metabo-
lism-related gene expression of mice on an atherogenic diet. Journal of Hepatology, 49(6),
1019-1028.
www.sciencedirect.com/science/article/pii/S0168827808006053

Alberdi, G., Rodrguez, V. M., Miranda, J., Macarulla, M. T., Churruca, I., & Portillo, M. P.
(2013). Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats.
Food chemistry, 141(2), 1530-1535.
www.sciencedirect.com/science/article/pii/S0308814613004287

Baile, C. A., Yang, J. Y., Rayalam, S., Hartzell, D. L., Lai, C. Y., Andersen, C., & DellaFera, M.
A. (2011). Effect of resveratrol on fat mobilization. Annals of the New York Academy of Sci-
ences, 1215(1), 40-47.
www.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2010.05845.x/full

Baur,J.A., Pearson, K.J., Price, N. L.,Jamieson, H.A., Lerin, C., Kalra,A., ... & Sinclair, D.A. (2006). Res-
veratrol improves health and survival ofmice on a high-calorie diet. Nature, 444(7117), 337-342.
www.nature.com/nature/journal/v444/n7117/abs/nature05354.html

Timmers, S., Konings, E., Bilet, L., Houtkooper, R. H., van de Weijer, T., Goossens, G. H., ... &
Schrauwen, P. (2011). Calorie restriction-like effects of 30 days of resveratrol supplementation
on energy metabolism and metabolic profile in obese humans. Cell metabolism, 14(5), 612-622.
www.sciencedirect.com/science/article/pii/S155041311100386X

Davinelli, S., Sapere, N., Visentin, M., Zella, D., & Scapagnini, G. (2013). Enhancement of
mitochondrial biogenesis with polyphenols: combined effects of resveratrol and equol in
human endothelial cells. Immunity & Ageing, 10(1), 28.

Ungvari, Z., Sonntag, W. E., de Cabo, R., Baur, J. A., & Csiszar, A. (2011). Mitochondrial pro-
tection by resveratrol. Exercise and sport sciences reviews, 39(3), 128.
www.ncbi.nlm.nih.gov/pmc/articles/PMC3123408/

Scarpulla, R. C. (2008). Transcriptional paradigms in mammalian mitochondrial biogenesis

and function. Physiological reviews, 88(2), 611-638.
www.physrev.physiology.org/content/88/2/611.short

Puigserver, P., & Spiegelman, B. M. (2003). Peroxisome proliferator-activated receptor-

coactivator 1 (PGC-1): transcriptional coactivator and metabolic regulator. Endocrine
reviews, 24(1), 78-90.
www.press.endocrine.org/doi/abs/10.1210/er.2002-0012

T3 Fuel
 17

Kaufman, B. A., Durisic, N., Mativetsky, J. M., Costantino, S., Hancock, M. A., Grutter, P., &
Shoubridge, E. A. (2007). The mitochondrial transcription factor TFAM coordinates the as-
sembly of multiple DNA molecules into nucleoid-like structures. Molecular biology of the
cell, 18(9), 3225-3236.
www.molbiolcell.org/content/18/9/3225.short

Aquilano, K., Vigilanza, P., Baldelli, S., Pagliei, B., Rotilio, G., & Ciriolo, M. R. (2010). Peroxi-
some Proliferator-activated Receptor Co-activator 1 (PGC-1) and Sirtuin 1 (SIRT1) Re-
side in Mitochondria POSSIBLE DIRECT FUNCTION IN MITOCHONDRIAL BIOGENESIS.
Journal of Biological Chemistry, 285(28), 21590-21599.
www.jbc.org/content/285/28/21590.short

Popovici, D., Mihai, N., & Urbanavicius, V. (1979). Abnormalities of oxidative phosphoryla-
tion due to excess of deficiency of thyroid hormones. Endocrinologie, 18(3), 143-147.
www.europepmc.org/abstract/MED/7433860

Nicolson, G. L. (2013). Mitochondrial dysfunction and chronic disease: treatment with nat-
ural supplements. Altern Ther Health Med, 20(1), 18-25.

Piper, B. F., Lindsey, A. M., & Dodd, M. J. (1987). Fatigue mechanisms in cancer patients:
developing nursing theory. In Oncology nursing forum (Vol. 14, No. 6, p. 17).
www.ncbi.nlm.nih.gov/pubmed/3320981

Logan, A. C., & Wong, C. (2001). Chronic fatigue syndrome: oxidative stress and dietary
modifications. Alternative medicine review: a journal of clinical therapeutic, 6(5), 450-459.
www.europepmc.org/abstract/MED/11703165

Marcovina, S. M., Sirtori, C., Peracino, A., Gheorghiade, M., Borum, P., Remuzzi, G., & Ar-
dehali, H. (2013). Translating the basic knowledge of mitochondrial functions to metabolic
therapy: role of L-carnitine. Translational Research, 161(2), 73-84.
www.sciencedirect.com/science/article/pii/S1931524412003672

Reuter, S. E., & Evans, A. M. (2012). Carnitine and Acylcarnitines. Clinical pharmacokinetics,
51(9), 553-572. www.link.springer.com/article/10.1007/BF03261931#page-1

Malaguarnera, M., Cammalleri, L., Gargante, M. P., Vacante, M., Colonna, V., & Motta, M. (2007).
L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive
functions in centenarians: a randomized and controlled clinical trial. The American journal of
clinical nutrition, 86(6), 1738-1744. www.ajcn.nutrition.org/content/86/6/1738.short

T3 Fuel
 18

Premawardhana, L. D. K. E., & Lazarus, J. H. (2008). Disorders of the thyroid gland. Special-
ist Training in Endocrinology, 59.

Maia, A. L., Goemann, I. M., Meyer, E. L. S., & Wajner, S. M. (2011). Type 1 iodothyronine
deiodinase in human physiology and disease deiodinases: The balance of thyroid hormone.
Journal of Endocrinology, 209(3), 283-297.

Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., ... & Woe-
ber, K. A. (2012). Clinical practice guidelines for hypothyroidism in adults: cosponsored by
the American Association of Clinical Endocrinologists and the American Thyroid Associa-
tion. Endocrine Practice, 18(6), 988-1028.
www.aace.metapress.com/content/611883025v735392/

Fatourechi, V. (2009, January). Subclinical hypothyroidism: an update for primary care phy-
sicians. In Mayo Clinic Proceedings (Vol. 84, No. 1, pp. 65-71). Elsevier.
www.sciencedirect.com/science/article/pii/S0025619611608094

Soriguer, F., Gutirrez-Repiso, C., Rubio-Martin, E., Linares, F., Cardona, I., Lpez-Ojeda,
J., ... & Garca-Fuentes, E. (2011). Iodine intakes of 100300 g/d do not modify thyroid
function and have modest anti-inflammatory effects. British Journal of Nutrition, 105(12),
1783-1790. www.ncbi.nlm.nih.gov/pubmed/21262066

Patrick, L. (2008). Iodine: deficiency and therapeutic considerations. Alternative medicine

review: a journal of clinical therapeutic, 13(2), 116-127.
www.europepmc.org/abstract/MED/18590348

Papp, L. V., Lu, J., Holmgren, A., & Khanna, K. K. (2007). From selenium to selenoproteins:
synthesis, identity, and their role in human health. Antioxidants & redox signaling, 9(7),
775-806. www.online.liebertpub.com/doi/abs/10.1089/ars.2007.1528

Stapleton, S. R. (2000). Selenium: an insulin mimetic. Cellular and Molecular Life Sciences CMLS,
57(13-14), 1874-1879. www.link.springer.com/article/10.1007/PL00000669#page-1

Frnsinn, C., Englisch, R., Ebner, K., Nowotny, P., Vogl, C., & Waldhusl, W. (1996). Insulin-
like< i> vs.</i> non-insulin-like stimulation of glucose metabolism by vanadium, tungsten,
and selenium compounds in rat muscle. Life sciences, 59(23), 1989-2000.
www.sciencedirect.com/science/article/pii/S0024320596005504

Prasad, A. S. (1994). Zinc: an overview. Nutrition (Burbank, Los Angeles County, Calif.),
11(1 Suppl), 93-99. www.europepmc.org/abstract/MED/7749260

T3 Fuel
 19

Abreu, I. A., & Cabelli, D. E. (2010). Superoxide dismutasesa review of the metal-associ-
ated mechanistic variations. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics,
1804(2), 263-274. www.sciencedirect.com/science/article/pii/S1570963909003367

Prasad, A. S. (2008). Clinical, immunological, anti-inflammatory and antioxidant roles of

zinc. Experimental gerontology, 43(5), 370-377.
www.sciencedirect.com/science/article/pii/S0531556507002458

Galbo, H., Hummer, L., Petersen, I. B., Christensen, N. J., & Bie, N. (1977). Thyroid and tes-
ticular hormone responses to graded and prolonged exercise in man. European journal of
applied physiology and occupational physiology, 36(2), 101-106.
www.link.springer.com/article/10.1007/BF00423117#page-1

Jansen, J., Rosenkranz, E., Overbeck, S., Warmuth, S., Mocchegiani, E., Giacconi, R., ... &
Rink, L. (2012). Disturbed zinc homeostasis in diabetic patients by< i> in vitro</i> and< i> in
vivo</i> analysis of insulin-mimetic activity of zinc. The Journal of nutritional biochemistry,
23(11), 1458-1466. www.sciencedirect.com/science/article/pii/S0955286311002750

Ilouz, R., Kaidanovich, O., Gurwitz, D., & Eldar-Finkelman, H. (2002). Inhibition of glycogen
synthase kinase-3 by bivalent zinc ions: insight into the insulin-mimetic action of zinc.
Biochemical and biophysical research communications, 295(1), 102-106.
www.sciencedirect.com/science/article/pii/S0006291X02006368

Brookins Danz, E. D., Skramsted, J., Henry, N., Bennett, J. A., & Keller, R. S. (2009). Resvera-
trol prevents doxorubicin cardiotoxicity through mitochondrial stabilization and the SIRT1
pathway. Free Radical Biology and Medicine, 46(12), 1589-1597.
www.sciencedirect.com/science/article/pii/S0891584909001543

Leonard, S. S., Xia, C., Jiang, B. H., Stinefelt, B., Klandorf, H., Harris, G. K., & Shi, X. (2003).
Resveratrol scavenges reactive oxygen species and affects radical-induced cellular respons-
es. Biochemical and biophysical research communications, 309(4), 1017-1026.
www.sciencedirect.com/science/article/pii/S0006291X03017327

Budanov, A. V., Sablina, A. A., Feinstein, E., Koonin, E. V., & Chumakov, P. M. (2004). Regen-
eration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science,
304(5670), 596-600. www.sciencemag.org/content/304/5670/596.short

Jin, S. H., Yang, J. H., Shin, B. Y., Seo, K., Shin, S. M., Cho, I. J., & Ki, S. H. (2013). Resveratrol
inhibits LXR-dependent hepatic lipogenesis through novel antioxidant< i> Sestrin2</i>
gene induction. Toxicology and applied pharmacology, 271(1), 95-105.
www.sciencedirect.com/science/article/pii/S0041008X13001786

T3 Fuel
 20

Ghosh, S., Liu, B., & Zhou, Z. (2013). Resveratrol activates SIRT1 in a Lamin A-dependent man-
ner. Cell Cycle, 12(6), 872-876. www.landesbioscience.com/journals/cc/2012CC4683R.pdf

Lakshminarasimhan, M., Rauh, D., Schutkowski, M., & Steegborn, C. (2013). SIRT1 activa-
tion by resveratrol is substrate sequence-selective. Aging (Albany NY), 5(3), 151.
www.ncbi.nlm.nih.gov/pmc/articles/PMC3629287/

Lakshminarasimhan, M., Curth, U., Moniot, S., Mosalaganti, S., Raunser, S., & Steegborn, C.
(2013). Molecular architecture of the human protein deacetylase SIRT1 and its regulation
by AROS and resveratrol. Bioscience reports, 33(3), 395-404.
www.bioscirep.org/bsr/033/bsr033e037.htm

Singh, B. K., Sinha, R. A., Zhou, J., Xie, S. Y., You, S. H., Gauthier, K., & Yen, P. M. (2013).
FOXO1 Deacetylation Regulates Thyroid Hormone-induced Transcription of Key Hepatic
Gluconeogenic Genes. Journal of Biological Chemistry, 288(42), 30365-30372.
www.jbc.org/content/288/42/30365.short

Timmers, S., Hesselink, M. K., & Schrauwen, P. (2013). Therapeutic potential of resvera-
trol in obesity and type 2 diabetes: new avenues for health benefits?. Annals of the New
York Academy of Sciences, 1290(1), 83-89. www.onlinelibrary.wiley.com/doi/10.1111/
nyas.12185/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false

Timmers, S., Konings, E., Bilet, L., Houtkooper, R. H., van de Weijer, T., Goossens, G. H., ... &
Schrauwen, P. (2011). Calorie restriction-like effects of 30 days of resveratrol supplementa-
tion on energy metabolism and metabolic profile in obese humans. Cell metabolism, 14(5),
612-622. www.sciencedirect.com/science/article/pii/S155041311100386X

Poulsen, M. M., Jrgensen, J. O. L., Jessen, N., Richelsen, B., & Pedersen, S. B. (2013). Res-
veratrol in metabolic health: an overview of the current evidence and perspectives. Annals
of the New York Academy of Sciences, 1290(1), 74-82.
www.onlinelibrary.wiley.com/doi/10.1111/nyas.12141/abstract?deniedAccessCustomise
dMessage=&userIsAuthenticated=false

Akieda-Asai, S., Zaima, N., Ikegami, K., Kahyo, T., Yao, I., Hatanaka, T., ... & Setou, M. (2010).
SIRT1 regulates thyroid-stimulating hormone release by enhancing PIP5K activity through
deacetylation of specific lysine residues in mammals. PloS one, 5(7), e11755.
www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0011755#pone-
0011755-g007

T3 Fuel
 21

Hubbard, B. P., Gomes, A. P., Dai, H., Li, J., Case, A. W., Considine, T., ... & Sinclair, D. A.
(2013). Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Sci-
ence, 339(6124), 1216-1219. www.sciencemag.org/content/339/6124/1216.short

Garfinkel, L., & Garfinkel, D. (1984). Magnesium regulation of the glycolytic pathway and the
enzymes involved. Magnesium, 4(2-3), 60-72. www.ncbi.nlm.nih.gov/pubmed/2931560

Parmar, H. S., & Kar, A. (2009). Protective role of< i> Mangifera indica</i>,< i> Cucumis
melo</i> and< i> Citrullus vulgaris</i> peel extracts in chemically induced hypothyroidism.
Chemico-biological interactions, 177(3), 254-258.
www.sciencedirect.com/science/article/pii/S0009279708006248

Fatourechi, V. (2009, January). Subclinical hypothyroidism: an update for primary care phy-
sicians. In Mayo Clinic Proceedings (Vol. 84, No. 1, pp. 65-71). Elsevier.
www.sciencedirect.com/science/article/pii/S0025619611608094

Haase, H., Overbeck, S., & Rink, L. (2008). Zinc supplementation for the treatment or pre-
vention of disease: current status and future perspectives. Experimental gerontology, 43(5),
394-408. www.sciencedirect.com/science/article/pii/S0531556507002987

Triggiani, V., Tafaro, E., Giagulli, V. A., Sabba, C., Resta, F., Licchelli, B., & Guastamacchia, E.
(2009). Role of iodine, selenium and other micronutrients in thyroid function and disorders.
Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-
Immune, Endocrine & Metabolic Disorders), 9(3), 277-294.
www.ingentaconnect.com/content/ben/emiddt/2009/00000009/00000003/art00006

Betsy, A., Binitha, M. P., & Sarita, S. (2013). Zinc deficiency associated with hypothyroidism:
an overlooked cause of severe alopecia. International journal of trichology, 5(1), 40.
www.ncbi.nlm.nih.gov/pmc/articles/PMC3746228/

Kralik, A., Eder, K., & Kirchgessner, M. (1996). Influence of zinc and selenium deficiency
on parameters relating to thyroid hormone metabolism. Hormone and metabolic research,
28(05), 223-226.
www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2007-979169

Nishiyama, S., Futagoishi-Suginohara, Y., Matsukura, M., Nakamura, T., Higashi, A., Shinohara,
M., & Matsuda, I. (1994). Zinc supplementation alters thyroid hormone metabolism in disabled
patients with zinc deficiency. Journal of the American College of Nutrition, 13(1), 62-67.
www.tandfonline.com/doi/abs/10.1080/07315724.1994.10718373#.U_tp2_mwLOo

T3 Fuel
 22

Taneja, S. K., & Mandal, R. (2008). Beneficial effect of modified egg* on serum T3, T4 and
dyslipidaemia following dietary Zn-supplementation in Wistar rat. Indian journal of experi-
mental biology, 46(3), 171. www.nopr.niscair.res.in/handle/123456789/4449

Khrle, J. (1995). Thyroid hormone deiodinases--a selenoenzyme family acting as gate

keepers to thyroid hormone action. Acta Medica Austriaca, 23(1-2), 17-30.
www.europepmc.org/abstract/MED/8767511

Nussey, S. S., & Whitehead, S. A. (2013). Endocrinology: an integrated approach. CRC Press.
www.books.google.com/books?hl=en&lr=&id=pjZvmnZpKXsC&oi=fnd&pg=PR11&dq=E
ndocrinology:+An+Integrated+Approach.+Oxford:+BIOS+Scientific+Publishers%3B+200
1&ots=nEUzSzDewx&sig=enXc0CQgg5QO692NACWd46EinH4#v=onepage&q=Endocr
inology%3A%20An%20Integrated%20Approach.%20Oxford%3A%20BIOS%20Scientif-
ic%20Publishers%3B%202001&f=false

Videla, L. A., Fernndez, V., Tapia, G., & Varela, P. (2006). Thyroid hormone calorigenesis and
mitochondrial redox signaling: upregulation of gene expression. Frontiers in bioscience: a
journal and virtual library, 12, 1220-1228. www.ncbi.nlm.nih.gov/pubmed/17127375

Laurberg, P. (1984). Mechanisms governing the relative proportions of thyroxine and 3, 5,

3-triiodothyronine in thyroid secretion. Metabolism, 33(4), 379-392.
www.sciencedirect.com/science/article/pii/0026049584902038

Maxwell, C., & Volpe, S. L. (2007). Effect of zinc supplementation on thyroid hormone func-
tion. Annals of Nutrition and Metabolism, 51(2), 188-194.
www.karger.com/Article/FullText/103324

Benvenga, S., Amato, A., Calvani, M., & Trimarchi, F. (2004). Effects of carnitine on thyroid
hormone action. Annals of the New York Academy of Sciences, 1033(1), 158-167.
www.onlinelibrary.wiley.com/doi/10.1196/annals.1320.015/abstract?deniedAccessCusto
misedMessage=&userIsAuthenticated=false

Benvenga, S., Ruggeri, R. M., Russo, A., Lapa, D., Campenni, A., & Trimarchi, F. (2001). Use-
fulness of l-carnitine, a naturally occurring peripheral antagonist of thyroid hormone ac-
tion, in iatrogenic hyperthyroidism: a randomized, double blind, placebo-controlled clinical
trial. The Journal of Clinical Endocrinology & Metabolism, 86(8), 3579-3594.
www.press.endocrine.org/doi/abs/10.1210/jcem.86.8.7747

T3 Fuel