Thermogenic Dietary Supplements

1
Thermogenic Dietary Supplements

• Michael F. Criqui
• LT, MSC, USN
• Nutrition Programs Officer
• Physical Readiness Program
• Navy Personnel Command
• Presented to the ShipShape Facilitators
• 25 June 03

2
Talking Points

• Background and Definitions
• PRIMS Data on Overweight Sailors
• Review of Popular Thermogenic Compounds
• GNC Former Top 5
• Web Sites

3
Background

• In 1999 dietary supplements were a multi-million
  dollar industry
• In 2003 dietary supplements are a multi-billion
  dollar industry
• Dietary supplement consumption has increased in
  the general population and in the military
• The medical community has a responsibility to
  provide guidance to the warfighter for all issues
  related to dietary supplements

4
Definition

• Thermogenic - relates to the production of heat
  in the body
• Adipose tissue - is a major site for
  thermogenesis
• Thermogenic supplements - are consumed with the
  intent of causing a breakdown in fat and an
  increase in energy expenditure
• Several clinical studies - have shown certain
  thermogenic substances or the combination to be
  efficacious in promoting weight loss BUT AT WHAT
  COST?

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Why do Sailors Take Supplements?

• Must maintain body fat standards
• Produced by a society where 61 of U.S. adults
  were either overweight or obese with a BMI of gt
  25/ gt30 respectively
• Career success depends on ability to meet BCA
  standards
• Have not learned or adopted a fitness lifestyle
• Heavily marketed (EAS spent 32 million 2002)

CDC 1999
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PRIMS Data Using BMI

• DODI 1308 has set upper allowable BMI limit at
  27.5

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Percent Body Composition Failures as of 5/1/03
N250K
N150K
N160K
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Popular Thermogenic (Weight Loss) Compounds

Ephedra Yohimbe
Caffeine Conjugated Linoleic Acids
Green Tea Ginseng
Bitter Orange (Synephrine) Galega Officinalis
7-Keto DHEA Coleus Forskohlin Commiphora Mukul
Garlic
Touted as thermogenic or additive in larger
formula
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Ephedra

• What is it?
• Ephedrine (synthetic form) normally occurs as an
  extract from herbal ephedra/Ma Huang
• How does it work?
• Stimulates SNS mimicking epinephrine increasing
  cardiac output, muscle contraction,
  bronchodilation
• Acts as a beta-2-agonist binding to
  ß-adrenoreceptors prompting metabolism, heat
  production, contractility
• Thermogenesis acts on ß-receptors in adipose
  tissue breaking down and mobilizing fat as fuel

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Ephedra

• Effectiveness?
• Rand Report Of 550 ephedra articles 20 met the
  research criteria for weight loss. Control group,
  gt 8 weeks (six categories)
• Ephedrine vs. P (1.3 greater loss/mo x 4 mo)
• Ephedrine C vs. P (2.2greater loss/mo x 4 mo)
• E C vs E alone (0.8 greater loss in EC)
• Ephedra vs. P (1.8 greater loss/mo x 3 mo)
• Ephedra Caffeine Herbs vs. P (2.1 greater
  loss/mo x 4 mo)

http//www.fda.gov/OHRMS/DOCKETS/98fr/95n-0304-bk
g0003-ref-07-01-index.htm
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Ephedra

• Effectiveness?
• Only 1 study lasted greater than 6 month
• No studies assessed post intervention weight
  maintenance
• Safety?
• 27 vs 29 attrition T vs C
• in subjects irritability, anxiety, insomnia, N/V,
  palpitations, tachycardia, HTN, headache
• in all reports 84 deaths, 26 MI, 56 CVA, 30
  other cardiac events

http//www.fda.gov/OHRMS/DOCKETS/98fr/95n-0304-bk
g0003-ref-07-01-index.htm
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Ephedra

• Safety cont
• (Gurley 2000) assessed ephedra content of 10
  commercially available ephedra products using
  HPLC
• 19 of 20 contained ephedra
• Pseudoephedrine was found in 16 samples ranging
  from 0.16 to 9.45 mg per capsule
• In lot to lot comparisons differences in alkaloid
  content ranged from 44 to 1000
• Common dosage?
• Ephedrine 20mg 3 x d or Ephedra herb 6 solution
  (325mg). Often combined with C in a 110 ratio

Gurley, BJ, Gardner SF, Hubbard, MA. Content
versus label claims in ephedra containing
supplements. Am J Health Syst Pharm
200057963-969.
13
Caffeine

• What is it?
• Classified as a trimethylxanthine found in
  virtually every culture is the most widely
  consumed herbal
• How does it work?
• Stimulates CNS and the release of epinephrine
  from adrenal glands. Mobilizes fatty acids for
  fuel and may have fat oxidizing effect for weight
  loss
• Effectiveness?
• A weak thermogenic effect alone. (Greenway 2000)
  combined 20mg C with 10 mg Ephedrine in obese
  females

Greenway FL, et al. The effect of an herbal
dietary supplement containing ephedrine and
caffeine on oxygen consumption in humans. J
Altern Complement Med 20006(6)553-555.
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Caffeine

• Effectiveness?
• Treatment group expended 2 more kcal/min vs
  placebo group.
• Translates to 90 extra kcal expended in 45 min
  without exercise or dieting
• Safety?
• Nausea, heart palpitations, headache, muscle
  tension
• Common dosage?
• Ranges from 1.8 to 3 mg/pound body weight

15
Green Tea

• What is it?
• Second only to water in worldwide consumption,
  made from picked leaves that are lightly steamed
• How does it work?
• Contains antioxidants such as polyphenols and
  catechins. Most notably Epigallocatechin (EGCG).
• Effectiveness?
• Dulloo (1999) noted a mild thermogenic effect
  with GT consumption 50 mg caffeine and EGEC 90mg.
  GT was significantly better than C alone or P in
  elevating metabolism at rest. GT raised fat
  metabolism by 4 (80 Kcal)/24 hrs.
• Dulloo (2000) found mechanism due to interaction
  b/t catechin and caffeine

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Green Tea

• Interaction thought to inhibit breakdown of
  norepinephrine
• Safety?
• Reported wide margin of safety. Twenty cups in a
  day have been tolerated w/o side effects other
  than SX associated with XS caffeine
• GT may interact with medications and prolong
  bleeding time
• Common dosage?
• Range from 125-500 mg/d of an extract
  standardized to at least 60 polyphenols and/or
  EGCG.
• This should be equivalent to 4-10 cups of brewed
  tea/day

Dulloo Ag, 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
Dec70(6)1040-5.
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Bitter Orange (Synephrine)

• What is it?
• Found in the fruit of a plant known as Citrus
  aurantium or zhi shi.
• How does it work?
• A stimulant chemically similar to C E thought
  to suppress appetite, boost energy and increase
  metabolic rate w/o deleterious effects seen in
  CNS stimulant ephedrine.
• Main ingredient in ephedra free products due to
  its metabolic pathway (beta-3 agonist vice
  beta-1, beta-2 or alpha-1 in ephedra).
• Effectiveness?
• Shows promise in animal studies in reducing brown
  adipose tissue but no substantial research has
  been conducted in humans who have no BAT

Dullo Ag, et. Al. Green tea and thermogenesis
interactions between catechin-polyphenols,
caffeine and sympathetic activity. Int J Obes
Relat Metab Disord. 2000 Feb24(2)252-8.
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Bitter Orange (Synephrine)

• Effectiveness?
• May act in concert with ingredients tyramine and
  octopamine to provide a mild stimulant effect.
  This is theorized to promote weight loss via
  appetite suppression.
• Safety?
• Synephrine and citrus aurantium elevate blood
  pressure in animal studies and should be avoided
  in individuals with cardiovascular concerns such
  as hypertension
• Common dosage?
• Synephrine is a small component of citrus
  aurantium. A standardized extract of 4-20 mg
  synephrine/d found in typical dose of 200-600 mg
  of standardized citrus aurantium extract (3-6
  synephrine)

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7-Keto DHEA

• What is it?
• A close relative of DHEA, 7-keto (3
  Acetyl-7-Oxo-dehydroepiandrosterone) is several
  steps removed from testosterone
• How does it work?
• DHEA taken for its anti-aging effect has been
  linked to hormone sensitive cancers. 7-Keto DHEA
  is thought to be a safe alternative as a
  thermogenic aid.
• Effectiveness?
• Touted as a non-androgenic or estrogenic
  version of DHEA.
• Animal studies showed promise as a weight-loss
  aid from thermogenic properties

Carpene C, et al. Selective activation of beta-3
adrenoreceptors by octopaminecomparative studies
in mammalian fat cells. Naunyn Schmiedebergs Arch
Pharmacol. 1999 Apr359(4)310-21.
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7-Keto DHEA

• Effectiveness?
• Human studies did not show ergogenic or
  thermogenic effect
• Safety?
• Animal and in vitro research prompted two human
  trials with doses of 200mg per day. No
  beneficial effects were found though dosage was
  well tolerated
• Common dosage?
• Two human trials used 200 mg/day though
  commercial supplements typically provide 50 mg.

Bobyleva, V. The effects of the ergosteroid
3-acetyl-7-oxo-dehydroepiandrosterone on
mitochondrial membrane potential possible
relationship to thermogenesis. Archives of
Biochemistry and Biophysics, 341(1)May 122-128,
1997.
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Corleus Forskolin

• What is it?
• A derivative of the mint family. Used in SE Asia
  as a spice and for treatment of heart ailments
  and stomach cramps
• How does it work?
• Theorized to stimulate adenylate cyclase
  cAMP in the fat cell hormone sensitive lipase
  to breakdown fat stores.
• Effectiveness?
• CF has been shown to stimulate cAMP levels in a
  test tube but there have been no peer-reviewed
  human studies assessing effectiveness via oral
  administration.

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Corleus Forskolin

• Safety?
• Unknown. Could cause adverse effects in people
  taking anti-coagulant medications and or
  hypertensive meds.
• Children and pregnant/lactating women should
  avoid
• CF has potential to interact with various cells
  of the body and is not recommended as a
  supplement
• Common dosage?
• Typical dosage recommendations (from company
  owning the patent) for fat loss is 60 mg/day.
• Extract ranges from 1-10 forskohlin. Label
  reading Coleus forskoli (10 extract) -250 mg
  equaling 25 mg of forskohlin.

23
Yohimbe

• What is it?
• The active ingredient Yohimbine comes from the
  bark of a tree in Africa
• How does it work?
• A purified extract yields an alkaloid stimulant
  similar to caffeine and ephedra. Fx as a CNS
  stimulant, MAOI to increase levels of
  norepinephrine. Can block alpha-2 adrenergic
  receptors and increase fat oxidation.
• Effectiveness?
• Sax (1991) tested a six month oral dose of 43 mg
  yohimbine and found no beneficial effects on body
  weight , body fat or lipid levels

Sax, L. Yohimbine does not affect fat
distribution in men. Int J Obes
199115(9)561-565.
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Yohimbe

• Effectiveness?
• More efficacious in the treatment of sexual
  dysfunction than weight loss with 30 reporting
  improvement in sexual function
• Safety?
• Concern over safety is raised because of reported
  toxicity of yohimbine. Headaches, anxiety,
  tension, HTN, elevated HR and hallucinations are
  reported side effects.
• More effective and safe supplements exist and
  therefore yohimbe is generally not recommended.
• Common dosage?
• Accepted standardized dosages do not exist but 20
  mg/d has been studied. Doses gt40 mg/day can
  result in adverse side effects

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Conjugated Linoleic Acids

• What is it?
• Derived from the essential fatty acid, linoleic
  acid
• How does it work?
• Thought to interact with prostaglandins, derived
  from fatty acid molecules and elevate synthesis
  of growth hormone enhance muscle growth and fat
  loss
• Effectiveness?
• Very effective in pigs, mice, rats and chickens
  when placed in feed.
• Mild benefit noted in overweight subjects who
  loss 2-4 pounds when supplemented with 3-4
  grams/day for 12-weeks.

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Conjugated Linoleic Acids

• Effectiveness?
• More research must be conducted to determine
  effectiveness in humans.
• Safety?
• Gastrointestinal discomfort reported in 30 of
  subjects supplemented with 3-5 grams/day.
• Common Dosage?
• Most people consume 1 gram/day in their diet from
  meat and dairy.
• Typical supplemental dose ranges from 3-5 grams
  per day

Benito, P et al. The effect of conjugated
linoleic acid on plasma lipoproteins and tissue
fatty acid composition in humans. Lipids. 2001
Mar36(3)229-36.
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Ginseng

• What is it?
• Adaptogenic herbs from the Araliacae family.
  Normally Panax Ginseng or Siberian ginseng
• How does it work?
• An adaptogen is therapeutic and restorative tonic
  thought to help cope with stress.
• 1200 mg of Panax ginseng improved mood and
  markers of stress in nurses working night shift
• Thermogenic benefits have been predicted but only
  shown in laboratory rodents
• Rats exposed to cold and given ginseng have
  developed a thermogenic response to acute
  hypothermia

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Ginseng

• Effectiveness?
• Ginseng has been studied for its ability to
  protect cells from damage, act as an antioxidant,
  protect against cancer, regulate BP and stimulate
  metabolism.
• Shown to be effective in helping the body cope
  with stress but not as a thermogenic aid
• Safety?
• Generally considered safe with a few caveats.
  Careful in hypertensive people or those with low
  blood sugar
• Supplementation not recommended to exceed 3
  months duration
• Common Dosage?
• 1-2 g/d as a dried root in American ginseng, 2-3
  g/d Siberian ginseng

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• As of June 2003 all ephedra containing products
  will be removed from GNC shelves

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Top 5 Sellers
1. XenadrineTM?
Xenadrine 120 Caps, Serving Size 2, Servings per
Container 60Nutritional FactsServing size 2
Capsules Amount Per Serving Pantothenic Acid
(vitamin B5) 40 mg Bitter Orange 85 mg MaHuang
335 mg Guarana Extract 910 mg White Willow Bark
Extract 105 mg Ginger Root 50 mg Proprietary
ThermoSynergist Blend (L-Tyrosine, Acetyl
L-Carnitine, Fisetin, Magnesium, Phosphate, DMAE)
225 mg
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Top 5 Sellers
2. Ripped Fuel?
Supplement FactsServing Size 2
CapsulesServings per container 60 MaHuang
Extract (Ephedra)...............334mg(standardiz
ed for 20mg ephedra) Guarana.....................
.......................910mg(standardized for
22 caffeine) L-Carnitine........................
................100mgChromium Picolinate.........
................200mcg
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Top 5 Sellers
Supplement FactsServing Size Amount 3
CapsulesServings Per Container 23 Calcium(as
hydroxycitrate)..........................265mgChr
omium(as Polynicotinate).........................1
33mcgPotassium (as Chloride/ Hydroxycitrate).....
.....................249mg Hydroxagen
Plus............................1.7gGarcinia
Cambogia (fruit rind) extractStandardized for
(-)hydroxycitrate acidGlucomannan
(Amorphophallus Konjac)Alpha Lipoic AcidWillow
Bark Extract (purple white)standardized for
saliconL-Carnitine (as Tartrate)Hydroxy
TeaGreen Tea Leaf ExtractStandardized for 95
polyphenols 70 catechins (45 epigallocatechin
gallate - 90 mg EGCG)Caffeine (as Cafeine
Anhydrous)Guarana Extract (seed)Standardized
for 200mg of caffeine
3. Hydroxycut?
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Top 5 Sellers
Supplement FactsServing Size 3
CapsulesServings per container 40
Chromium.......................................2
00mcg(from chromium picolinate)MaHuang
Extract................................334mg(aeri
al parts) (Standardized for 20 mg ephedra
alkaloids)Guarana Seed Extract...................
.....909mg(standardized for 22
caffeine)CitriMax................................
...........500mg(Garcinia Cambogia Rind
Extract)L-Carnitine..............................
.........100mg(from L-carnitine
L-tartrate)Potassium Phosphate
Monobasic...........75mgMagnesium Phosphate
Tribasic.............25m
4. Diet Fuel?
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Top 5 Sellers
5. Thermicorel?
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Web Sites

• www.supplementwatch.com
• www.naturaldatabase.com
• www.dietary-supplements.info.nih.gov
• www.herbs.org
• www-nehc.med.navy.mil/hp
• chppm-www.apgea.army.mil

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Texts

• Sports Supplements (Antonio, Stout) 2001
• The Health Professionals Guide to Popular Dietary
  Supplements (Sarubin A) 2002
• Performance Enhancing Substances in Sport and
  Exercise (Bahrke, Yesalis) 2002