Supplement Edge
By Anssi H. Manninen, MHS
The Most Effective Supplements for Fat Loss
Obesity results from an excess of energy intake over energy
expenditure. So, if the obese individual wants to shred extra lard, the solution
is extremely simple: Energy expenditure must exceed energy intake for a
suitable length of time. Obviously, this message is simple only in principle, but
very difficult to put into practice. Indeed, more than half of the adult American
population must now be classified as overweight or obese.
Thus, it’s not surprising the market is flooded with hundreds of
products that promise to shed extra lard quickly and easily. Unfortunately, it’s
not easy to find objective information on these products. Even articles found
in the various sports magazines that support the use of herbals and dietary
supplements for fat loss are often commercially biased.
With that said, this article reviews the scientific rationale behind the
most popular thermogenic (fat-burning) supplements.
Thermogenesis and Extra Lard: A Short Course
There are two types of fat tissue: white fat tissue and brown fat tissue.
When we talk about body fat, we refer to white fat tissue (i.e., lard). White fat
tissue has a number of functions in the body that include mechanical
cushioning (e.g., around some internal organs) and thermal insulation, but its
main role is that of storing food energy in the form of triglycerides and
releasing it in the form of free fatty acids when it’s needed by other tissues.
However, brown fat tissue has a unique metabolic feature.
Not all the energy in foods is transferred to adenosine triphosphate (ATP; the
universal energy carrier in each cell). Instead, a portion of this energy
becomes heat. On average, 35 percent of the energy in foods becomes heat
during ATP formation. However, in brown fat, sympathetic nervous
stimulation (“fight-or-flight” response) causes liberation of large amounts of
heat. Brown fat tissue is the major site of heat production (thermogenesis) in
the newborn and is especially prominent in the mammalian fetus. The largest
accumulation of brown fat tissue envelops the kidneys and adrenal glands.
The mass of brown fat tissue peaks at birth and gradually decreases during
the early weeks of life.
Brown fat contains a large number of mitochondria (powerhouses of
the cell) and many small globules of fat instead of one large fat globule. In
these cells, the process of oxidative phosphorylation (formation of ATP by
using energy derived from an electron transport to oxygen) in the
mitochondria is mainly “uncoupled.” That is, when the cells are stimulated by
the sympathetic nerves, the mitochondria produce a large amount of heat but
almost no ATP. Therefore, almost all the released oxidative energy
immediately becomes heat. The important bottom line is that radiating energy
away as heat enables the body to spend, rather than store, energy.
Since the process of uncoupling dissipates metabolic energy, there
has been great interest in this process in relation to regulation of body weight:
If we could stimulate uncoupling, it would be a wonderful way to burn extra
lard. Indeed, a possible link between obesity and deficient brown fat function
has been researched. For example, evidence indicates that thermogenesis is
defective in instances of obesity.
Two types of external stimuli trigger thermogenesis: 1) the ingestion of
food and 2) prolonged exposure to cold temperature, both of which stimulate
the tissue via sympathetic innervation via the hormone norepinephrine
(noradrenaline). The sympathetic signals increase the size of brown fat
tissue. (For a more detailed review on brown fat tissue and thermogenesis,
see reference #3).
How Do Scientists Determine the Effectiveness of Thermogenic
Supplements?
The gold standard in scientific research design is a prospective,
double-blind, randomized, placebo-controlled clinical study. Simply stated,
subjects are randomized to either treatment (thermogenic supplementation)
or a control group (fake supplementation) and followed from that point.
Obviously, the metabolic rate (i.e., energy expenditure) must be
measured. There are two basic approaches. First, scientists can measure
directly the heat liberated by the body (direct calorimetry). However, that
requires sophisticated equipment, so the alternative approach is that of
indirect calorimetry. In this approach, energy expenditure is assessed from
measurement of the burning of fuels, which are in turn assessed from the
whole-body consumption of oxygen and production of carbon dioxide. An
indirect calorimeter can be constructed in the form of a room in which a
subject may live a relatively normal life.
If you are still awake, it’s finally time to examine the rationale behind
the thermogenic supplements.
Ephedrine + Caffeine: Most Popular Thermogenic Stack
Clearly, ephedrine is— or at least was— the most popular thermogenic
supplement known to mankind. Ephedrine is classified as a sympathomimetic
drug and central nervous system stimulant. In most dietary supplements,
ephedrine used to appear as an extract from one of two herbs: ephedra or Ma
Huang.
Although ephedra species have a long tradition of use (more than
5,000 years) for respiratory ailments, the FDA recently decided to ban
ephedra-containing supplements. The pharmacokinetics (i.e., the
characteristic interactions of a drug and the body in terms of its absorption,
distribution, metabolism and excretion) of ephedrine following ingestion of
supplements formulated as concentrated ephedra extracts is distinguishable
from that of synthetic ephedrine found in conventional dosage forms.
Nevertheless, the FDA did not ban ephedrine.
Ephedrine has also been coupled with both caffeine and aspirin to
further enhance its effectiveness (i.e., ECA). Ephedrine stimulates release of
noradrenaline, which stimulates the synthesis of prostaglandins by the
activated tissues. Aspirin inhibits the synthesis of prostaglandins and serves
as a prostaglandin blocker, and thereby may prevent inhibition of
norepinepherine release.
The history of ephedrine as a weight loss agent is rather interesting. In
1972, Dr. Erikson, a Danish general practitioner in Elsinore, Denmark, noted
unintentional weight loss when he prescribed a compound containing
ephedrine, caffeine and Phenobarbital to patients he was treating for asthma.
By 1977, over 70,000 patients were taking the “Elsinore Pill,” and one Danish
pharmaceutical house was producing one million tablets a week!
Early commercial ephedra-caffeine supplements were extremely
popular among serious athletes simply because they worked and had few, if
any, adverse effects when used as directed. Indeed, numerous wellcontrolled studies support this contention. For example, Dr. Boozer and
colleagues at the New York Obesity Research Center reported that in a sixmonth placebo-controlled trial, ephedra plus caffeine promoted bodyweight
and body fat reduction and improved blood lipids without significant adverse
effects.
More recently, a new study by Dr. Greenway and co-workers at the
Pennington Biomedical Research Center examined the effect of a
supplement containing herbal caffeine and ephedrine on metabolic rate,
weight loss, body composition and safety parameters. Results indicated that
ephedra plus caffeine promoted more weight and fat loss than placebo (fake
supplement) and was well tolerated. According to the authors, “Dietary herbal
supplements containing [ephedra and caffeine] should remain available to
obese individuals trying to control their weight.”
When it comes to purported adverse effects, Dr. Soni and co-workers
concluded that the adverse event reports raise concerns about the risks
associated with ephedra usage, but did not establish a direct causal
relationship between intake of ephedra and reported injuries. They also
pointed out that the published preclinical and clinical studies, and the long
history of safe use of ephedra, support the safety-in-use of ephedra when
used as directed. According to Dr. Soni et al., the problems associated with
the adverse events appear to be the result of overuse, inconsistent potency,
individual sensitivity, contaminations, etc.
In summary, ephedrine-caffeine supplementation promotes fat loss
and is relatively safe when used as directed. However, ephedrine/ephedra is
certainly not for everyone and must be used responsibly. For example, it
should be never, under any circumstances, be used by someone with heart
disease or high blood pressure. If you decide to use ephedrine/ephedra, it’s
very important that you read product labels, warnings and cautions, and
follow the directions.
Caffeine + Nicotine: The Super Thermogenic Stack?
It’s well established that nicotine replacement therapy limits weight
gain after smoking cessation. So, Dr. Anna Jessen and colleague at the Royal
Veterinary and Agricultural University in Denmark examined the acute
thermogenic effects of chewing gum containing different doses of nicotine and
caffeine. This well-controlled study included 12 healthy, normal-weight men.
Energy expenditure was measured with indirect calorimetry before and 2.5
hours after subjects chewed the gum.
The results indicated that one milligram of nicotine has a pronounced
thermogenic effect, which is increased by about 100 percent when it’s
combined with 100 milligrams of caffeine. Further, no side effects were
reported with the gum that contained one milligram of nicotine with 50 or 100
milligrams of caffeine. Nevertheless, if you want to give this stack a try, talk
with your doctor first.
Capsiate: The Latest Thermogenic
The capsicum species, native to tropical America, incorporates such
peppers as the cayenne, red and chili. Chili is the Aztec name for the
cayenne pepper, and it has been used by Native Americans as food and
medicine for over 9,000 years.2
The medicinal properties of capsicum are attributable to a compound
known as capsaicin, although other capsaicinoids are also available.
Capsaicin is regarded as a pain reliever, possibly blocking pain fiber by
depleting substance P, the neurotransmitter mediating pain signals to the
brain.
Further, capsaicin has been reported to 1) elevate body temperature;
2) stimulate the secretion of catecholamines (noradrenaline, adrenaline); 3)
promote energy expenditure; and 4) suppress body fat accumulation in
experimental animals. However, capsaicin is strongly pungent and
neurotoxic, which largely prohibits its administration to humans.
Dr. S. Yazawa and co-workers reported that CH-19 Sweet, a nonpungent cultivar of Capsicum annuum L, rarely contains pungent
capsaicinoids, but contains a large amount of two capsaicinoid-like
substances. The chemical structures of these two substances have been
identified and named capsiate and dihydrocapsiate by Dr. Kobata and
colleagues.
Recently, Dr. Masuda Yoriko and colleagues from Japan examined
whether continuous administration of capsiate promotes energy expenditure
in mice.9 They measured respiratory gas by indirect calorimetry. Results
indicated that oxygen consumption (i.e., energy expenditure) was significantly
higher in the capsiate group than in the control group. Also, carbohydrate and
fat burning was significantly higher in the capsiate group than in the control
group. Consequently, the mean bodyweight of mice in the capsiate group was
significantly lower than that of mice in the control group.
In summary, continuous administration of capsiate raises oxygen
consumption, an index of energy expenditure, suggesting that capsiatetreated mice burned more calories. The authors of this study concluded: “This
study suggests that capsiate, a non-pungent capsaicin analog, may be an
alternative to capsaicin for the therapeutic treatment of obesity in humans.”
However, well-controlled human studies are needed before firm conclusions
can be drawn.
Green Tea: Safe and Somewhat Effective
Dr. Abdul Dulloo and co-workers at the University of Geneva
investigated whether a green tea extract could increase 24-hour energy
expenditure and fat burning in humans. On three separate occasions,
subjects were randomly assigned among three treatments: green tea extract
(50 milligrams of caffeine and 90 milligrams of epigallocatechin gallate),
caffeine (50 milligrams) and placebo, which they ingested at breakfast, lunch
and dinner.
Results indicated that green tea ingestion resulted in a significant
increase in 24-hour energy expenditure. Investigators concluded: “Oral
administration of the green tea extract stimulated thermogenesis and fat
oxidation and thus has the potential to influence bodyweight and body
composition via changes in both [energy expenditure] and substrate
utilization.
Red Pepper + Caffeine: Promising Thermogenic Stack
Dr. M. Yoshioka and co-workers at Laval University in Canada
examined the effects of red pepper and caffeine ingestion on energy balance.
Investigators noted that red pepper + caffeine consumption significantly
reduced the cumulative ad libitum (self-directed) energy intake and increased
energy expenditure. The authors concluded, “The consumption of red pepper
and caffeine can induce a considerable change in energy balance when
individuals are given free access to foods.” Although these results are
intriguing, the long-term effectiveness and safety remain to be determined.
References
1. Groff JL, Gropper SS. Advanced Nutrition and Human Metabolism.
Belmont, CA: Wadsworth/Thomson Learning, 2000.
2. Frayn KN. Metabolic Regulation: A Human Perspective. Oxford,
UK: Blackwell Science, 2003.
3. Cannon B, Nedergaard J. Brown adipose tissue: function and
physiological significance. Physiol Rev, 84:277-359, 2004. Free
full-text paper available at www.physiology.org
4. Rawson ES, Clarkson PM. Ephedrine as an ergogenic aid. In:
Bahrke MS, Yesalis CE, eds. Performance-Enhancing Substances
in Sports and Exercise. Champaign, IL: Human Kinetics, 2002, pp.
289-298.
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weight loss: a 6-month randomized safety and efficacy trial. Int J
Obesity, 2002;26:593-604.
7. Soni GM, Ioana GC, Griffiths JC, Burdock GA. Safety of ephedra:
lessons learned. Toxicol Letters, 2004;150:97-110.
8. Jessen AB, Toubro S, Astrup A. Effect of chewing gum containing
nicotine and caffeine on energy expenditure and substrate
utilization in men. Am J Clin Nutr, 2003; 77:1442-1447.
9. Masuda Y, Satoshi H, Kasumi O, et al. Up-regulation of uncoupling
proteins (UCPs) by oral administration of capsiate, a non-pungent
capsaicin analog. J Appl Physiol, Epub 2003 Sep 05.
10. Dulloo AG, Duret C, Rohrer D et al. Efficacy of a green tea extract
rich in catechin polyphenols and caffeine in increasing 24-h energy
expenditure and fat oxidation in humans. Am J Clin Nutr,
1999;70:1040-1045.
11. Yoshioka M, Doucet E, Drapeau V et al. Combined effects of red
pepper and caffeine consumption on 24 h energy balance in
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