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Interaction between energy drink ingredients and caffeine Stephen W. Schaffer University of South Alabama

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Interaction between energy drink

ingredients and caffeine

Stephen W. Schaffer University of South Alabama

Common constituents of energy drinks p g gy g

Red Bull Rockstar Monster Full Throttle

Calories 220 280 200 220

Carbohydrates 54 g Sucrose, glucose

62 g Sucrose, glucose

54 g Sucrose, glucose, sucralose, maltodextrin

57 g High-fructose corn syrup, sucrose

Sodium Only listed as sodium citrate

80 mg sodium citrate 360 mg 16% RDA Sodium citrate, sodium chloride

160 mg Sodium citrate

Caffeine 160 mg 160 mg Part of a 1.35-g “energy blend”

Only listed as part of a 5000-mg “energy blend”

141 mg Part of a 3000-mg “energy blend”

Taurine 2000 mg 2000 mg Part of a 1.35-g “energy blend”

2000 mg Part of a 5000-mg “energy blend”

Only listed as part of a 3000-mg “energy blend”

Glucuronolactone Only listed (1200 mg)[b] None listed Only listed as part of a 5000-mg “energy blend”

None listed

Red Bull Rockstar Monster Full Throttle

Niacin (B3) 200% RDA Niacinamide (40 mg)[b]

40 mg 200% RDA Niacinamide

40 mg 200% RDA Niacinamide

100% RDA Niacinamide

Inositol (B8) Only listed 50 mg Part of a 1.35-g “energy blend”

Only listed as part of a 5000-mg “energy blend”

None listed

Pyridoxine hydrochloride (B6) 500% RDA (10 mg)[b] 4 mg 200% RDA 4 mg 200% RDA 200% RDA

Cyanocobalamin (B) 160% RDA Listed as vitamin B12 (10μg)[b]

12 Hg 200% RDA 12 Hg 200% RDA 200% RDA

Riboflavin (B2) None listed 6.8 mg 400% RDA 3.4 mg 200% RDA None listed

Pantothenic acid (Bs) 100% RDA Calcium pantothenate (10 mg)[b]

20 mg 200% RDA Calcium pantothenate

None listed None listed

Vitamin content of energy drinks

Natural extracts of energy drinks Red Bull Rockstar Monster Full Throttle

Ginseng extract None listed 50 mg Part of a 1.35-g “energy blend”

400 mg Only listed as part of a 3000-mg “energy blend”

Guarana extract None listed 50 mg Part of a 1.35-g “energy blend”

Only listed as part of a 5000-mg “energy blend”

Only listed as part of a 3000-mg “energy blend”

Ginkgo biloba leaf extract None listed 300 mg Part of a 1.35-g “energy blend”

None listed None listed

Milk thistle extract None listed 40 mg Part of a 1.35-g “energy blend”

None listed None listed

D-glucuronolactone

Glucuronolactone is added to energy drinks to improve mood and diminish fatigue.

Glucuronic pathway

Dietary source of glucuronolactone

• 1. Dietary exposure from naturally occurring substances – 1-2 mg/day, but average individual will consume about 38 mg/day

• 2. Mean exposure for average energy drink consumer – 126 mg/day

• 3. Heavy energy drink consumers (95th percentile) – 840-900 mg/day

Pharmacokinetics of glucuronolactone

• 1. Plasma levels peak 1-2 hrs after oral administration in rats.

• 2. D-glucuronolactone is preferentially metabolized by the pentose pathway; xylulose, xylitol and glucardiac acid can be detected in the urine.

• 3. Glucuronic acid is a component of connective tissue.

Glucuronolactone toxicity • 1. The Scientific Committee on Food

evaluated a 13 week oral toxicity study in rats administered D-glucuronolactone (0, 300, 600, 1000 mg/kg bw/day) . Mild cytoplasmic vacuoles were detected in the kidney. However, no vacuolization was detected in a follow-up study although some focal inflammation of the kidney was observed.

Taurine

Taurine is involved in bile acid conjugation, osmoregulation, neuronal

excitability, inflammation and mitochondrial function.

Pathological symptoms of taurine deficiency

• 1. Retinopathy • 2. Cardiomyopathy • 3. Myopathy • 4. Immune deficiency • 5. Developmental defects

Taurine consumption

» Adults Adolescent Children • Omnivore diet 40-400 mg/day • Ave. energy drink 272 283 278 • consumer • Heavy energy 2000 2300 1400 • Drink consumer • (95 percentile)

Pharmacokinetics of taurine

Sved et al., Amino Acids 32:459-66, 2007

Ave. consumer – 21 mg/kg

Sved et al., Amino Acids 32:459-66, 2007

• Taurine (3-6g) has been administer-ed daily to a large number of pa-tients (including adults, children and even infants). No adverse health effects have been noted.

• The EFSA Journal 935: 1-31, 2009 • (European Food Safety Authority)

• Is there an interaction between taurine and caffeine relative to diuresis and natriuresis?

Taurine as a diuretic

Mozaffari and Schaffer, J Cardiovasc Pharmacol 37: 742-750, 2001

Diuretic potential of taurine/caffeine combination

Riesenhuber et al., Amino Acids 31: 81-83, 2006

• Is there an interaction between taurine and caffeine relative to blood pressure and heart rate?

Effect of taurine on blood pressure and heart rate

Mozaffari et al., Kidney Int 70: 329-337, 2006 Yamori et al., J Biomed Sci 17 (Suppl 1):S6, 2010

Effect of taurine/caffeine combination on BP and HR

Bichler et al., Amino Acids 31: 471-476, 2006

• Do taurine and caffeine interact to

potentiate cardiac arrhythmias?

Eby and Halcomb, Med Hypotheses 67: 1200-4, 2006

• A common cause of ectopic heart

beats is ingestion of caffeine. Arrhythmias are also produced by nutrient deficiencies, such as that of taurine. Taurine administration can suppress arrhythmias by altering ion flux (Ca, K and Na) or dampening sympathetic activity.

Antiarrhythmic activity of taurine

Vascular effects of taurine

Abebe, Life Sci 82: 279-289, 2008

• Do taurine and caffeine interact to

cause seizures?

Inhibition of picrotoxin-mediated seizures by taurine

L’Amoreaux et al, J Biomed Sci 17(Supp 1):S14, 2010

Stimulation of GABA production by taurine

• Brain levels Taurine GABA • (umol/g wet wt) • Control 228 + 4.3 67 + 7.1 • Tau-fed 224 + 4.6 95 + 2.5 • Tau-injected 216 + 6.2 76 + 7.8

• El Idrissi et al. , Adv Expt Biol Med 526: 515-525, 2003

• Effect of herbal supplements on cardiovascular and CNS function

J Prim Health Care. 2012 Jun 1;4(2):163-4. Guarana: Paullinia cupana, P. sorbilis; also known as Brazilian cocoa and 'zoom'. Woods DJ. Source School of Pharmacy, University of Otago, Dunedin, New Zealand. [email protected] Abstract The main constituent of guarana is caffeine, with smaller quantities of theophylline and theobromine. There is no evidence that the berries or extracts contain anything else that is therapeutically useful.Guarana is associated with many therapeutic properties, but there is no evidence to support these other than effects that can be attributed to caffeine. Guarana is widely available in herbal products and energy drinks. Excessive intake can cause the same effects as too much caffeine.

Interaction of ginsenoside-Rg1 with the glucocorticoid receptor

Lee et al., Mol Cell Endocrinol 133:135-40, 1997

Effect of ginseng on blood pressure of SHRs

Hong et al., J Agric Food Chem 60: 3086-91, 2012

Effect of ginseng on pilocarpine-induced seizures

Lian et al., Epilepsia 46: 15-22, 2005

Effect of Ginkgo biloba on vascular function

• 1. An extract of Ginkgo increases cerebral blood flow in rats (Krieglstein et al., Life Sci 39: 2327-34, 1986).

• 2. Extract inhibits platelet activating factor and phospholipase A2, but the compound affecting platelets is not abundant in extract (Braquet & Cedemin, Am J Gastroenterol 88: 2138, 1993).

Distribution of caffeine exposure in children, and teenagers

Seifert et al., Pediatrics 127: S11-28, 2011

Other possible interactions involving energy drinks in children

• 1. 2.5 million US children take stimulants for attention-deficit/hyperactivity disorder. Interaction between energy drinks and those stimulants deserve consideration.

• 2. Ciprofloxacin used in children with cystic fibrosis inhibit caffeine metabolism.

• A case report by Jones et al. (Jones et al., Epilepsy & Behavior 10:504-8, 2007) implicate energy drinks in initiation of seizures, but there are no studies examining the effect of simultaneous taurine and caffeine feeding on seizure activity.

Caffeine composition of various beverages and energy drinks

Effect of taurine-Mg on cesium-induced arrhythmias

Yin et al., Biol Trace Elem Res 146: 192-198, 2012

Effect of taurine on NE outflow of mesenteric artery

Hano et al., Adv Expt Med Biol 643: 57-63, 2009