The cardiovascular system 7

CHAPTER CONTENTS collapse (eucalyptus) and congestive heart failure (wormwood)

(Eimas 1938; Gurr & Scroggie 1965; Grieve 1978; Weisbord
The heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
et al 1997). Damage to the heart has been seen after fatal doses
Heart rate and rhythm . . . . . . . . . . . . . . . . . . . 111
of wintergreen and wormseed oils (Eimas 1938; Opdyke 1976
Blood pressure . . . . . . . . . . . . . . . . . . . . . . . . . 112 p. 713–715).
Animal and ex vivo studies . . . . . . . . . . . . . . . . 112 Heart activity is dependent upon the movement of calcium
Convulsants . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 ions into myocardial cells, and substances that inhibit this
Calcium channel blockade . . . . . . . . . . . . . . . . . . 113 influx, the so-called calcium channel blockers, have a depressant
Undefined mechanisms . . . . . . . . . . . . . . . . . . . . 113 effect on the heart. They act on slow calcium channels to reduce
Human oral studies . . . . . . . . . . . . . . . . . . . . . 114 contractility and electrical conduction in the heart. They also act
Inhalation effects . . . . . . . . . . . . . . . . . . . . . . 114 on vascular smooth muscle to reduce vascular tone (see Calcium
Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . 114
channel blockade below). Bisabolol, carvacrol, b-caryophyllene
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . 115
oxide, eugenol, (þ)-carvone, ()-menthol, thymol and possibly
Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 (E)-anethole, block calcium channels in cardiovascular cell
Thrombocytes . . . . . . . . . . . . . . . . . . . . . . . . 115 membranes (Schafer et al 1986; Teuscher et al 1989; Sidell
Erythrocytes . . . . . . . . . . . . . . . . . . . . . . . . . 116 et al 1990; Sensch et al 2000; Damiani et al 2004; Magyar
Glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 et al 2004). The same effect has been observed with peppermint
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 oil (Hills & Aaronson 1991). In addition, b-caryophyllene oxide
strongly inhibited potassium ion fluxes, while eugenol exerted a
smaller effect (Sensch et al 2000).
The cardiovascular system comprises the heart, the blood, and Thujone had a depressant action on the isolated rabbit heart,
the vessels through which blood flows. The heart is a pump affecting both systole and diastole. A preliminary fall in pressure
whose function is to ensure that the body tissues receive ade- was followed by a rise, and these were explained in terms of a
quate blood to supply their need for oxygen, glucose, fats, amino direct action on heart muscle, and an action on the vasomotor
acids and other nutrients. In addition, the rate of blood flow out center, respectively (Florey and Student, 1968).
of the tissues must be sufficient to remove waste products and
toxins, and to prevent fluid accumulation.
Heart rate and rhythm
A depressant effect on dog heart has been observed following
The heart the iv administration of 1–2 mL per kg doses of a “saturated
solution” of sage oil in 33 alcohol (equivalent to 18.9% v/v eth-
There are very few known effects of essential oils on the heart, anol) (Caujolle & Franck 1945a). Geraniol, thymol and ()-
except when taken in overdose. Cardiovascular consequences of carvone all had a depressant action on frog heart function, when
human poisoning from various essential oils include irregular a 10% aqueous emulsion was injected into the femoral lym-
heartbeat (tansy), rapid heartbeat (wintergreen), cardiovascular phatic sac, e.g., geraniol has an effect at 180 mg/kg or higher,

© 2014 Robert Tisserand and Rodney Young.

http://dx.doi.org/10.1016/B978-0-443-06241-4.00007-2
 Essential Oil Safety
but not at 90 mg/kg (Lysenko 1962). These findings imply that
only high doses of these constituents affect the heart. Camphor
produced a rise in heart rate in isolated rabbit heart, via a direct
effect on heart muscle (Christensen and Lynch 1937). In
humans, the predominant effect on the heart appears to be
depressant. However, one report suggests that camphor can
sensitize the heart to epinephrine (adrenaline) (Saratikov et al
1957).
The only known negative effects from essential oils in mod-
erate doses apply to menthol and peppermint. Mentholated
cigarettes and peppermint confectionery have been linked to
cardiac fibrillation in patients prone to the condition while
being maintained on quinidine, a stabilizer of heart rhythm
(Thomas JG 1962). This might be explained by an interaction
between menthol and quinidine, but no precedent for this could
be found. Bradycardia (slowing of heartbeat) has been reported
in an individual addicted to menthol cigarettes (Luke 1962).
Menthol-rich oils (cornmint and peppermint) should probably
be avoided altogether in cases of cardiac fibrillation.
Blood pressure
Pressure in the blood circulatory system varies according the
phases of the cardiac cycle, and the proximity of the different
vessels to the heart. It is regulated principally by the rate and
force of contraction of the heart, by the caliber of the resistance
vessels, mainly the arterioles, and by the volume of blood in the
system. Blood pressure (BP) is at its highest in the aorta and
other main arteries when the ventricles contract (in systole)
and is at its lowest when the ventricles are relaxed (in diastole),
as well as in the veins and venules throughout the cardiac cycle.
There is an ongoing debate about the relationship between
BP and cardiovascular disease. It is now thought that the risk
of cardiovascular disease begins when systolic and diastolic pres-
sures are 115 and 75 mmHg, respectively, and that this doubles
with each increment of 20 and 10 mmHg, respectively. It has
also been suggested that individuals with systolic and diastolic
readings of 120–139 and/or 80–89 mmHg, respectively, should
Table 7.1 Essential oils reputed to raise blood pressure in aromatherapy texts
Essential oil Valnet 1964 Tisserand 1977 Franchomme & Pénöel 1990
Black pepper – –
Camphor – √
Eucalyptus – –
Hyssop √ √
Peppermint – –
Rosemary √ √
Sage √ –
Thyme √ –
Valnet 1964 p. 220, 260, 272, 288; Tisserand 1977 p. 201–204; Franchomme & Pénöel 1990 p. 374; Battaglia 1997 p. 295; Davis P 1999 p. 153; Pitman 2004 p. 343.
112
be classified as prehypertensive, and may need to adopt
health-promoting lifestyle changes (Chobanian et al 2003).
Any excessively elevated or prolonged increase in BP (hyper-
tension) is undesirable because it increases the work of the heart
and can lead to irreversible changes to organs including the blood
vessels, heart, kidneys and brain. The most common form of
hypertension (in 90–95% of cases) is known as ‘primary’ or
‘essential’ hypertension, where no single causal factor can be
identified. Rather, a number of predisposing or risk factors
are likely to be present, including smoking, excessive drinking
of alcohol, a stressful life, poor diet and lack of exercise. Some
people have a genetic predisposition to hypertension (Coy
2005; Imumorin et al 2005).
Temporary fluctuations in BP are normal and harmless in a
healthy individual. They may be due to a variety of factors such
as psychosocial demands or changes in physical activity. It
should be stressed that psychological factors can play a role in
raising or lowering BP (Whyte 1983; Linden & Moseley
2006). Substance use can also lead to the elevation of BP, salt
and caffeine being two examples. In a hypertensive individual,
though small fluctuations may not be harmful, regular, moder-
ate increases can be damaging.
Animal and ex vivo studies
The essential oils most commonly cited in aromatherapy texts
as being contraindicated in hypertension are hyssop, thyme,
rosemary and sage (Table 7.1). Similar advice is repeated in
other books and on many websites, but very little supporting
evidence could be found in the scientific literature. The original
source for this information appears to be Valnet (1990), first
published in French in 1964. In this text, the four essential oils
are claimed to be hypertensive, and in each case two references
are given. One is Caujolle & Franck (1944b), but this is a mis-
take since this paper concerns lavender, lavandin and spike lav-
ender oils only. The other reference is a thesis by R. Cazal,
published in 1944. We were not able to locate a copy of this.
Data on these and other essential oils are outlined below.
Battaglia 1997 Davis 1999 Pitman 2004
– – √ –
– – – –
– – – √
– √ √ √
√ – √ –
– √ √ √
– √ √ √
– √ – √

Convulsants
There is a complex relationship between convulsants and BP
(Freeman 2006). Intracranial hypertension can lower the
seizure threshold, and for example in eclampsia, both hyper-
tension and seizures are seen. In a report of nine distressed
neonates whose BP was continuously recorded, three had
generalized seizures, during which mean aortic pressure
increased dramatically (Lou & Friis-Hansen 1979). However,
a sudden drop in BP can also precipitate seizures (Agrawal &
Durity 2006).
When injected iv in convulsant doses, both wormwood oil
and hyssop oil produce a sudden drop, then rise in BP, the
convulsions coinciding with BP elevation. After apparently
extensive testing in cats, Coombs & Pike (1931) concluded that
‘oil of absinthe’ (wormwood oil) produced a hypotension that
initiated the seizures, and that the muscular contraction of
the seizures caused the spike in hypertension. BP dropped
below baseline after a seizure, and did not rise until the next
seizure took place. In some instances, doses below the con-
vulsive threshold caused a fall in BP that was so precipitous
it was fatal.
The type of wormwood oil used in this study is not stated,
but the commercially available oil was the b-thujone CT
(Parry 1922 p. 288; Guenther 1949–1952 vol 5 p. 494;
Arctander 1960 p. 661–663). The wormwood oil was diluted to
5% v/v in 95% ethanol, and the minimum convulsive dose was
0.08 mL/kg bw of the solution, so 0.004 mL/kg (3.6 mg/kg) for
the oil. Clonic convulsions were produced, with tonic limb
extension appearing at just under a lethal dose (Pike et al 1929).
Similarly, injecting dogs iv with 1–2 mL of a ‘saturated solution’
of hyssop oil in 33 alcohol resulted in an initial fall in BP, foll-
owed by a rise, accompanied by clonic convulsions, both lasting
3–4 minutes (Caujolle & Franck 1945b).
The convulsant constituents of wormwood oil and hyssop oil
are the thujones and pinocamphones, respectively. In cats,
camphor caused an initial fall in BP lasting 2–10 minutes,
followed by a rise of 8–30 mmHg above normal and lasting
for up to 30 minutes, when given intravenously at only
5 mg/kg (Christensen & Lynch 1937). Considering that this
was a sub-convulsant dose, the longer hypertensive phase is
interesting. However, whether camphor is hypotensive or
hypertensive has been debated for more than a century. Top-
ically applied camphor is likely to cause local vasodilation
(Futami 1984).
Sage oil, which can cause convulsions, contains varying
amounts of camphor and 1,8-cineole though camphor usually
predominates. When 1 g/kg of alcohol saturated with sage
oil was given iv to dogs there was no increase in BP, and in some
cases a slight fall was observed (Caujolle & Franck 1945a). An
intravenously administered aqueous-alcoholic extract of sage
caused a moderate but prolonged hypotensive effect in cats
(Todorov et al 1984).
In early 20th century reports, benzyl alcohol apparently
caused hypotension and convulsions in experimental animals
(MMWR 1982). In low birth weight infants exposed to benzyl
alcohol, toxic symptoms included respiratory distress and hypo-
tension (Benda et al 1986; Sreenan et al 2001). Many infants
also had central neural depression or seizures (Anon 1982).
The cardiovascular system CHAPTER 7
Calcium channel blockade
One proven way of lowering BP is to reduce the flow of calcium
ions into heart and vascular muscle using calcium channel
blockers. Apart from relaxing the heart, these drugs also reduce
the tone of the arteries and arterioles, thereby decreasing the
resistance to blood being pumped by the heart. Peppermint
oil and its major constituent (–)-menthol both have calcium
channel blocking actions. This explains why (–)-menthol dilates
systemic blood vessels after iv administration, and why pepper-
mint oil reduces smooth muscle spasm in the gut (Rakieten &
Rakieten 1957; Grigoleit & Grigoleit 2005b; Hawthorn et al
1988; Hills & Aaronson 1991).
A hypotensive action has been reported for thyme oil in a
Russian paper (Kulieva 1980). This is consistent with the cal-
cium channel blocking actions of its major constituents thymol
and carvacrol (Magyar et al 2004), and the hypotensive action of
carvacrol (Aydin et al 2007) and of topically applied thymol
(Futami 1984). We could find no information on peppermint
oil and BP, but topically applied menthol reduces blood pressure
for a short time through an effect on local tissues (Futami 1984;
Ragan et al 2004), and the calcium channel blocking effect of
both peppermint oil and menthol (cited above, under The
heart) makes a hypertensive action unlikely.
In mice, cinnamon bark oil caused variable changes in BP
after ip dosing at 100 mg/kg (Powers et al 1961). Cinnamal-
dehyde was hypotensive when administered to anesthetized
dogs at 5–10 mg/kg iv. In guinea pigs, a lower dose of 1 mg/
kg iv caused a small fall in BP. The authors inferred that
this action was mainly due to peripheral vasodilation mediated
by calcium channel blockade, similar to that caused by pap-
averine (Harada & Yano 1975). In a recent study, a range of
1 mM to 1 mM of cinnamaldehyde dose-dependently relaxed
prostaglandin F2a, norepinephrine and KCl-stimulated rat aorta.
It was suggested that a combination of endothelium-dependent
and -independent effects were responsible. One of the latter
mechanisms is thought to involve the blocking of calcium channels
(Yanaga et al 2006).
Undefined mechanisms
Other essential oil constituents with hypotensive actions caused
by direct vasodilation include, in order of decreasing potency,
linalool, citronellol, nerol, geraniol, a-terpineol and 1,8-cineole.
These compounds caused a 25% fall in systolic pressure, in doses
from 9.2–26.3 mg/kg, when administered iv to dogs in an emul-
sion (Northover & Verghese 1962). Intravenous 1,8-cineole was
dose-dependently hypotensive in normotensive rats at
0.3–10 mg/kg, and decreased heart rate at the highest dose
(Lahlou et al 2002a). Soares MC et al (2005) reported that
1,8-cineole probably has a calcium channel blocking action.
Spike lavender oil (28.0–34.9% 1,8-cineole) injected iv in
dogs resulted in a slight reduction in BP, followed by a rapid
return to normal (Caujolle & Franck 1944b). The essential oil
of Hyptis fruticosa was hypotensive in normotensive rats at
5–40 mg/kg iv, and caused concentration-dependent relaxation
of phenylephrine-stimulated isolated rat superior mesenteric
artery at 1–1000 mg/mL (Santos et al 2007). Although this oil
is not commercially available, it is interesting to note that it
113
 Essential Oil Safety
contains 16.8% 1,8-cineole, as well as 12.3% bicyclogermacrene
and 11.3% a-pinene (Menezes et al 2007). The action of euca-
lyptus oil will undoubtedly reflect that of 1,8-cineole.
Single iv injections of eugenol (1–10 mg/kg) elicited imme-
diate and dose-dependent hypotension in rats (Lahlou et al
2004), and similar results were found for eugenol-rich Ocimum
gratissimum leaf oil when given to hypertensive rats
(Interaminense et al 2005). Intravenous administration of either
1–20 mg/kg of Alpinia zerumbet leaf oil (40% terpinen-4-ol)
or 1–10 mg/kg of terpinen-4-ol, elicited dose-dependent
decreases in mean aortic pressure in rats (Lahlou et al
2002b). The hypotension induced by 1,8-cineole, eugenol or
tepinen-4-ol appears to be due to direct vascular relaxation,
rather than by affecting sympathetic tone. Northover &
Verghese (1962) reached the same conclusion.
Both geranium and lavender oils lowered BP in dogs when
administered iv in a ‘saturated alcoholic solution’ at 1–2 g/kg
(Clerc et al 1934). Similarly, an aqueous suspension of carrot
seed oil, injected iv into dogs, produced dose-dependent falls
in BP (Bhargava et al 1967). Taget oil was hypotensive in dogs,
reducing BP by up to 50% for 45 minutes after an iv dose of
50 mg/kg (Chandhoke & Ghatak 1969). Essential oils of angel-
ica (type unspecified), calamus, zedoary and tomar seed each
caused a transient fall in BP and heart rate when injected iv
into dogs at 0.01–0.05 mL/kg (Chopra et al 1954). Intravenous
doses of 0.2–1.6 mg/kg black seed oil dose-dependently
decreased arterial BP in rats (El Tahir et al 1993). This action
is in part due to the main constituent, thymoquinone, which
counteracted induced increases in systolic BP in rats when given
orally at 0.5 or 1 mg/kg/day (Khattab & Nagi 2007). In cats,
b-eudesmol at 10 mg/kg iv precipitated a hypotensive response
of 50–69% that lasted for 5–6 hours, but at a dose of 5 mg/kg iv,
there was no effect (Arora et al 1967).
(þ)-Limonene, which constitutes 16.4–24.4% of black pep-
per oil and 44.2% of white camphor oil, lowered monocrotaline-
induced pulmonary hypertension in rats, when given orally at
400 mg/animal/day for up to 21 days (Touvay et al 1995).
The farnesyltransferase inhibitory activity of limonene was sug-
gested as being linked to this action.
Human oral studies
In a clinical study, 14 of 15 hypertensive patients who ingested
0.45 mL/day of geranium oil for two months showed significant
improvement in their condition. They also showed a reduction
in cortisol levels (Nozaki 2001). Two small-scale controlled tri-
als showed preliminary clinical evidence for garlic oil having a
hypotensive action. When taken in capsules at 18 mg/day for
four weeks by normotensive volunteers, the oil reduced mean
(presumably systolic) pressure from 94 mmHg to 88 mmHg,
compared with a 2.3 mmHg mean reduction in the placebo
group in a two period, cross-over trial with 10 volunteers
per group. However, this ‘garlic oil’ was cold-pressed from fresh
garlic (Barrie et al 1987). A second randomized-controlled
trial in 27 normotensive trained male runners noted a mean
drop of 4.5 mmHg in systolic pressure following daily ingestion
of 2.3 mg steam-distilled garlic oil in capsules for 16 weeks
(Zhang et al 2001).
114
Inhalation effects
Temporary hypertension has been recorded following the
inhalation of certain of essential oils. Grapefruit, fennel, black
pepper or tarragon oil caused a slight increase of systolic BP
in humans after being inhaled for either three or seven minutes
(Haze et al 2002). It is feasible that these effects may have been
due to psychological factors. Human inhalation of ylang-ylang oil
caused a significant reduction in BP, which was thought to be
psychologically mediated (Hongratanaworakit & Buchbauer
2004). After 10 minutes of inhaling cedrol, both systolic and
diastolic pressures were reduced in healthy male and female
Japanese volunteers due to a reduction in sympathetic and an
increase in parasympathetic activity (Dayawansa et al 2003).
Conversely, inhalation of grapefruit oil for 10 minutes raised
BP in rats, due to the enhancement of sympathetic and the sup-
pression of parasympathetic activity (Shen et al 2005, Tanida
et al 2005). This appears to indicate a physiological effect.
Inhalation of lavender oil by rats resulted in a fall in mean
arterial BP, which is consistent with iv data cited above. The
effect was thought to be autonomically mediated, and was elim-
inated following induced anosmia (Tanida et al 2006). How-
ever, 30 minutes of lavender oil inhalation by 30 healthy
young men had no effect on BP, though other effects were seen
(Shiina et al 2008). In the summary of an article published in
Korean, once daily inhalation of a mixture of lavender, bergamot
and ylang-ylang oils for four weeks was said to lower BP in
patients with essential hypertension (Hwang 2006).
Both psychological and pharmacological processes were deter-
mined to be responsible for increases in BP in humans following
30 minutes inhalation of (þ)-limonene (systolic), (–)-limonene
(systolic), (þ)-carvone (diastolic), or (–)-carvone (systolic and
diastolic) (Heuberger et al 2001). For example, fragrance-induced
subjective ratings of increased alertness correlated significantly
with increases in BP. However, these same compounds, when
not administered by inhalation, may be hypotensive.
In a human study that prevented inhalation, 1 mL of 20%
sandalwood oil or a-santalol in peanut oil was applied to the
abdominal skin of volunteers, resulting in a small but significant
reduction in both systolic and diastolic pressures compared to
control subjects. This was presumably due to a physiological effect
resulting from transdermal absorption (Hongratanaworakit
et al 2004).
Discussion
Increases in BP have been recorded in both animals and humans
on essential oil administration, but it is not known whether any of
the data indicate a risk to people with hypertension. In all of the
cited studies, animals and humans with normal BP were tested.
Most of the early (1940s) research was carried out by injecting
dogs intravenously with moderately large doses of essential oils
diluted in ethanol. In some of these, the precise quantity of essen-
tial oil used is not known, since only the amount of the total solu-
tion is given. Both increases and decreases in BP were recorded.
Dermal administration of essential oil constituents can cause
reductions in BP due to local effects. Conversely, most inhalation
studies have reported BP increases.

Intravenous administration leads to a direct action on the
vascular system, which is primarily due to calcium channel
antagonism (Lahlou et al 2005). In inhalation studies, the
effects are autonomically mediated, and in humans, psy-
chological factors may come into play. In both rats and humans,
elevations of BP were seen in conditions that reflect those of
intentional and fairly intensive essential oil inhalation. Since soft
tissue massage reduces BP, the only potential risks seem to be
either from overdoses of certain convulsant essential oils, and
from intensive (as distinct from incidental) inhalation.
Oral garlic oil is possibly the most likely to reliably reduce high
BP, but there is no evidence that this would exacerbate an already
established hypotension. The action of garlic oil is clearly not due to
psychological factors nor, presumably, are the effects seen for
other essential oils in animal studies. However, in those involving
human inhalation, psychological factors are likely to play a part, and
the effects are autonomically mediated. In contrast, iv administra-
tion leads to a direct action on the vascular system, which is primar-
ily due to calcium channel antagonism (Lahlou et al 2005). A
formulation containing fenugreek oil inhibited angiotensin-
converting enzyme (ACE) in plasma and kidney when fed to male
alloxan-diabetic rats. ACE inhibitors are now commonly used in
the treatment of hypertension (Hamden et al 2011).
The mode of administration can play a significant role in the
resulting effect. For example, hypertension and convulsions can
both be caused by acute methyl salicylate poisoning. However,
topically applied methyl salicylate lowers BP through local
effects (Futami 1984; Ichiyama et al 2002; Dawson et al
2004). We have already seen that in rats, (þ)-limonene lowered
BP on iv injection, but raised it on inhalation. Since different
effects on BP seem to be possible from different methods of
administration, those from inhalation or dermal absorption
should not be assumed to reflect those of iv administration.
There is no research that shows whether the use of single or
blended essential oils can lead to a significant increase in BP dur-
ing an aromatherapy massage, but this seems unlikely since soft
tissue massage itself tends to reduce both systolic and diastolic
pressure (Holland & Pokorny 2001; McNamara et al 2003;
Aourell et al 2005).
Conclusion
Eucalyptus, camphor, pine, thyme and peppermint oils should
be scratched from cautionary lists. Hyssop and sage oils are only
a risk in convulsant oral doses, and lower doses are very likely to
be hypotensive. Therefore, they should not be contraindicated
in hypertension. It is likely that rosemary oil follows the same
pattern. Inhalation data suggest that essential oils presenting a
risk include grapefruit, lemon, caraway, black pepper, fennel,
tarragon and other oils high in carvone or limonene. However,
in the human studies the increases were only slight.
There is no clear evidence that essential oils have adverse
effects on the control of BP in humans. Some essential oils
may present a risk to some classes of hypertensive patient, in cer-
tain dose/route combinations, and there may be a theoretical
argument for exercising caution in certain cases of hypertension
and hypotension. However, until we know more about where the
risks lie, there is no case for contraindication of any essential oils.
The cardiovascular system CHAPTER 7
Blood
Blood is regarded as a circulating tissue. It consists of erythro-
cytes (red cells), leukocytes (white cells) and thrombocytes
(platelets) suspended in plasma, an aqueous medium containing
proteins and ions. Key functions of blood are to transport oxy-
gen, nutrients (including glucose) and hormones to different tis-
sues, and to transport carbon dioxide, metabolic waste products
and toxins away from tissues to the organs of excretion. Blood
also conducts heat around the body.
Blood disorders arise as a result of abnormal concentrations
of enzymes, hemoglobin or other proteins in plasma, or from
abnormalities in the structure of blood cells. These factors
can lead to impaired transport to and from the tissues with such
consequences as weakness, as well as susceptibility to infections
and decreased surveillance to pre-cancerous cells. As far as
essential oil constituents are concerned, effects on coagulation,
involving platelets, are the most common.
Defects in heme synthesis (which takes place in the liver and
bone) are discussed in Chapter 9, under Porphyrin production.
Thrombocytes
Thrombocytes (platelets) play an important role in hemostasis,
by plugging and repairing damaged blood vessels, thus prevent-
ing blood loss. They also participate in a cascade of events that
leads to blood clotting by triggering the release of a series of
coagulation factors. In the first step, platelets are activated by
various substances, including collagen from damaged tissue, as
well as ADP (adenosine diphosphate) and thromboxane A2,
secreted by activated platelets. Activation causes platelets to
become adhesive, which facilitates their attachment to dam-
aged tissues and to each other to form clumps. The penultimate
step in coagulation is the formation of fibrin from fibrinogen.
Fibrin filaments enmesh platelets and red and white blood cells
to form a plug, which contracts to form a clot. Because this is a
multi-step process, separate in vitro tests are often carried out
for inhibition of platelet aggregation by collagen, ADP, arachido-
nic acid, or other substrates.
Although the blood clotting mechanism is essential for con-
trolling blood loss, it can also lead to ischemic diseases such as
strokes and heart attacks, due to thrombosis and consequent
obstruction of blood flow. In order to maintain an optimal sup-
ply of blood to tissues, various mechanisms exist to prevent
excessive and counterproductive clotting.
Blood coagulation can be affected by a number of exogenous
substances, including essential oils, and can be a particular cause
of concern when administered in overdose. In a fatal case of
pennyroyal oil toxicity, there was bleeding from injection
sites as well as the vagina (Sullivan et al 1979). In other cases,
blood-thinning activity may result from relatively low doses.
In a small-scale trial with 20 healthy volunteers, a daily oral dose
of 18 mg cold-pressed garlic oil for four weeks reduced mean
platelet aggregation by 16.4% compared to placebo (Barrie
et al 1987). Both garlic and onion oils possess antiplatelet
activity, onion oil being more potent than garlic (Fenwick &
Hanley 1985). Since onion and leek oils share over 60% of their
115
 Essential Oil Safety
constituents, it seems likely that leek oil will possess a similar
action. Three constituents of garlic oil, diallyl sulfide, diallyl
disulfide and diallyl trisulfide, showed dose-dependent inhibi-
tion of ADP-induced aggregation of isolated human platelets
in vitro at 5–10 mM. At these concentrations, they also exhib-
ited a protective effect against glucose-induced oxidation in
erythrocyte membranes and platelets (Chan et al 2002).
Another constituent, methyl allyl trisulfide, also inhibits plate-
let aggregation (Boullin 1981; Fenwick & Hanley 1985).
In a report on the in vitro antiplatelet activity of 23 essential
oils, the most potent against a range of stimulants were Ocotea
quixos (a non-commercial oil containing 27.8% cinnamaldehyde
and 21.6% methyl cinnamate), Artemisia dracunculus (70%
estragole) and Foeniculum vulgare (75.8% (E)-anethole). Orig-
anum vulgare (54.4% carvacrol and 14.3% thymol), and Thymus
vulgaris (8.0% carvacrol and 6.8% thymol) oils were the most
potent inhibitors of arachidonic acid-induced platelet aggrega-
tion with IC50 values of 1.9 and 4.7 mg/mL, comparable with
that of aspirin. Among all 23 essential oils, antiplatelet and clot
dissolving activity correlated with their content of phenylpropa-
noid or phenolic constituents. Essential oils with a negligible
action included clary sage, cypress, lemongrass, rosemary, Dal-
matian sage Scots pine and turmeric (Tognolini et al 2006).
Inhibition of platelet aggregation has been confirmed for cin-
namaldehyde, (E)-anethole, estragole, eugenol, carvacrol and
thymol. Cinnamaldehyde inhibited the aggregation of human
platelets in vitro, and anticoagulant activity was seen in mice
after a combination of oral and ip dosing (Huang J et al
2007a). Confirmation of platelet aggregation has also been dem-
onstrated for (E)-anethole and estragole, which inhibited aggre-
gation of rabbit platelets induced by ADP, collagen or
arachidonic acid as potently as aspirin (Yoshioka & Tamada
2005). Both thymol and carvacrol inhibited arachidonic acid-
induced platelet aggregation, with potencies over 30 times
greater than that of aspirin. Thymoquinone, p-cymene, (–)-
menthol and (–)-menthone were virtually inactive (Enomoto
et al 2001).
The essential oil of Foeniculum vulgare and (E)-anethole both
demonstrated significant antithrombotic activity in vivo in mice
at oral doses of 30 mg/kg/day for five days. This may be due
antiplatelet and clot-destabilizing properties, in addition to a
vasorelaxant action (Tognolini et al 2007).
Dose-dependent antiplatelet activity, due to an antiprosta-
glandin action, was demonstrated by eugenol and isoeugenol,
which were both as potent as indomethacin. Myristicin, elemi-
cin and safrole were 100 to 1,000 times less potent, and linalool,
a-pinene, b-pinene, camphene, a-terpineol and terpinen-4-ol
were inactive (Rasheed et al 1984; Janssens et al 1990). Eugenol
similarly inhibited platelet aggregation induced by arachidonic
acid, collagen, epinephrine (adrenaline) or ADP (Chen SJ et al
1996). Inhibition of platelet aggregation has been reported for
verbenone and for ar-turmerone, but borneol, 1,8-cineole and
sabinene had no effect (Lee HS 2006; Chiariello et al 1986).
Both bergapten and imperatorin (the latter found at very low
levels in expressed lemon and lime oils) demonstrated strong
antiplatelet aggregation activity in vitro (Chen IS et al 1996).
There was a synergistic effect between the constituents of
lavandin grosso oil, in inhibiting platelet aggregation induced
by arachidonic acid, U46619, collagen and ADP, with IC50
116
values of 51, 84, 191 and 640 mg/mL, respectively. The major
constituents of the oil tested were linalyl acetate (36.2%), lin-
alool (33.4%), camphor (7.6%) and 1,8-cineole (5.8%), which
individually possessed only very weak antiplatelet activity in
the presence of the four agonists, compared to that of the whole
oil (Ballabeni et al 2004). Patchouli oil displays antiplatelet
activity, as does a-bulnesene, one of its major constituents
(Hsu et al 2006; Tsai et al 2007). b-Eudesmol is also signifi-
cantly active, reducing arachidonic acid-induced platelet aggre-
gation by 88% at 240 mM (Wang et al 2000).
Cornmint oil, menthol and menthone were found to be only
weak inhibitors of collagen and ADP-induced platelet aggrega-
tion with IC50 values in the millimolar range (Murayama &
Kumaroo 1986).
Acceleration of blood coagulation has been reported for allyl
isothiocyanate in rats, when given at 20 mg/kg/day iv for 7 days.
Blood coagulation time was decreased by 43%, which was
thought to be due to an increase in plasma phospholipids; this
effect was largely reversed by co-administration of thyroxine
(Idris & Ahmad 1975). However, the essential oil of Wasabia
japonica roots, which contains a number of isothiocyanates
including allyl isothiocyanate (79%), inhibited arachidonic
acid-induced rabbit platelet aggregation in vitro with an IC50
value of 112.1 mg/mL. Allyl isothiocyanate had an IC50 in the
same test of 1.7  103 M (Kumagai et al 1994).
Topically applied methyl salicylate can inhibit platelet aggre-
gation systemically (Tanen et al 2008). The anticoagulant drug
interaction issues with methyl salicylate are covered on Ch. 14,
p. 598. Methyl salicylate-rich essential oils should be avoided by
oral and non-oral routes.
We have contraindicated oral dosing of essential oils where
there is clinical evidence of coagulation inhibition (Box 7.1A).
We have cautioned oral dosing for essential oils with significant
in vitro data either for the essential oil, or for constituents occur-
ring at >25%: lavandin oil, leek oil, patchouli oil, and essential
oils containing (E)-anethole, carvacrol, cinnamaldehyde, estra-
gole, b-eudesmol, eugenol or thymol (Box 7.1B).
Erythrocytes
Erythrocytes (red blood cells) are responsible for carrying
oxygen to, and carbon dioxide from, tissues. To perform effi-
ciently, these cells must contain an optimum amount of
hemoglobin, which requires an adequate level of iron in the
body. A deficiency of iron and/or hemoglobin is a cause of
anemia, a condition characterized by symptoms such as fatigue,
shortness of breath on exertion and poor concentration due to
poor oxygenation of body tissues.
Casearia sylvestris essential oil, and two of its constituents,
b-caryophyllene (18.1%) and a-humulene (4.7%) caused signif-
icant hemolysis in human erythrocytes in vitro with maximal
concentrations not causing hemolysis (MCnH) values of
156.2, 96.3 and 98.9 mg/mL, respectively. Human erythrocytes
were among the most sensitive of seven species tested (Da Silva
et al 2008). Casearia sylvestris oil is not commercially pro-
duced. Thymoquinone, a major constituent of black seed oil,
triggered phospholipid scrambling and shrinkage of human
erythrocytes in vitro at 3 mM and above, after 48 hours
 The cardiovascular system CHAPTER 7

These erythrotoxic effects are part of a more general cytotoxic

Box 7.1 effect that may also impact cancer cells. We believe that there is
currently insufficient information for specific contraindications.
Essential oils that affect blood coagulation In contrast, some essential oil constituents have been shown to
A. Essential oils that are Cinnamon bark exert a protective effect on erythrocytes. For example, eugenol
known to, or are very Cinnamon leaf dose-dependently inhibited the hemolysis of erythrocytes
likely to, inhibit blood Clove bud induced by liver S9 fraction-treated carbon tetrachloride, pre-
coagulation sumably by protecting them from oxidative stress (Kumaravelu
Clove leaf
Birch (sweet) Clove stem et al 1996).
Garlic Fennel (bitter)
Onion Fennel (sweet)
Wintergreen Lavandin Glucose
B. Essential oils that Leek
may inhibit platelet Marigold (Mexican) Glucose is the body’s main source of energy, and therefore
aggregation based on Marjoram wild (carvacrol CT) blood glucose concentrations must be tightly controlled.
in vitro data either for Myrtle (aniseed) Numerous hormones contribute to this goal including glucagon
the oil or a major Oregano which increases blood concentrations, and insulin which
constituent decreases blood levels. If blood glucose levels fall below the nor-
Oregano (Mexican)
Ajowan mal range (hypoglycemia) a person may feel lethargic and expe-
Patchouli
Anise rience impaired mental functioning, or even brain damage in
Pimento berry
Anise (star) extreme cases. Chronic high blood levels (hyperglycemia)
Pimento leaf
Araucaria may implicate diabetes, which can be accompanied by such
Ravensara bark
Atractylis problems as eye, kidney, heart and/or nerve damage.
Savory
Basil (estragole CT) Several essential oils and constituents have been shown to
Tarragon
Basil (holy) exert hypoglycemic effects in animal models. A melissa oil with
Tejpat
Basil (Madagascan) an unusually high citral content (65.4% geranial and 24.7%
Thyme (borneol CT)
Basil (pungent) neral), when fed to male mice at 0.015 mg/day for six weeks,
Thyme (limonene CT)
Bay (W. Indian) caused a 65% reduction in blood glucose, a significant increase
Thyme (thymol and/or carvacrol
Bee balm (lemon) CTs) in serum insulin levels, and an improvement in glucose toler-
Cassia Thyme (spike) ance, compared to a control group. The authors explained this
Chervil by enhanced glucose uptake and metabolism in the liver and adi-
Oral administration of the above listed essential oils is either pose tissue, and inhibition of hepatic gluconeogenesis (Chung
contraindicated (list A) or cautioned (list B) in these circumstances: et al 2010). Similarly, gavage doses of 10, 15 or 20 mg/kg/day
• If taking anticoagulant drugs such as aspirin, heparin and warfarin citral for 28 days, dose-dependently lowered plasma insulin
• Breastfeeding mothersa levels and increased glucose tolerance in obese rats (Modak &
• Hemophilia Mukhopadhaya 2011). When a laboratory-distilled Tunisian
• Peptic ulcer geranium oil was given to alloxan-induced diabetic male rats
• Internal bleeding at 75 and 150 mg/kg/day po for 30 days, blood glucose was
• Severe hepatic or renal impairment reduced by an amount comparable with that elicited by gliben-
• Hypertensive or diabetic retinopathy clamide (600 mg/kg), while hepatic glycogen concentration
• Thrombocytopenia (decreased platelet count) increased (Boukhris et al 2012).
• Vasculitis Dietary fenugreek oil (for composition see Fenugreek
• Up to one week before or after major surgery or childbirth Profile, Chapter 13) fed to male alloxan-diabetic rats at 5%,
significantly inhibited a-amylase and maltase activity in the
a
This is precautionary, and is a controversial contraindication even within conventional pancreas and plasma. It also improved glucose tolerance and
medicine, for ‘novel’ anticoagulant drugs. If they are known to pass into breast milk, then
contraindication is very likely.
helped to protect pancreatic b-cells (Hamden et al 2011).
Turmeric oil dose-dependently inhibited glucosidase enzymes
more effectively than the antidiabetic drug acarbose. Its main
exposure, though loss of membrane integrity was not significant constituent, ar-turmerone (45.0–58.0%), showed potent
until 20 mM. These changes are precursors to hemolysis (Qadri a-glucosidase (IC50 ¼ 0.28 mg) and a-amylase (IC50 ¼ 24.5 mg)
et al 2009). Citral exhibited in vitro hemolytic activity in eryth- inhibitory activity (Lekshmi et al 2012).
rocytes (species not stated) at 3.0–5.9  104 M. A non-specific Myrtle oil reduced blood glucose by 51% in alloxan-diabetic
free radical-peroxide mechanism has been suggested (Segal & rabbits four hours after an oral dose of 50 mg/kg, but had no
Milo-Goldzweig 1985). effect on serum insulin concentrations (Sepici et al 2004). In
The essential oil of freshly distilled Tagetes minuta leaves rabbits, 50 mg/kg ip of black seed essential oil reduced blood
caused significant decreases in erythrocyte and hemoglobin levels glucose in fasting normal and alloxan-diabetic animals (Al-
when administered orally for 14 days to rats at 125 mL/kg bw. Hader et al 1993). Here again, the mechanism of action did
There were also increases in mean corpuscular volume, mean not appear to be insulin-mediated. Significant reductions in
corpuscular hemoglobin and neutrophils (Odeyemi et al 2008). blood glucose levels in both normal and alloxan-diabetic rats

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 Essential Oil Safety

were reported one hour following subcutaneous injections of dill

(type unspecified), sweet fennel, Dalmatian sage and white
Box 7.2
wormwood oils at 27, 21.5, 39 and 18.75 mg/kg, respectively
(Essway et al 1995). In contrast, Eidi et al (2005) found no sig- Essential oils that should be used with caution orally
nificant change in serum glucose levels in streptozotocin- in diabetic subjects whose blood glucose levels are
diabetic rats for up to five hours after ip administration of being controlled by orthodox drugs
0.042, 0.125, 0.2 or 0.4 mL/kg of Dalmatian sage oil. Anise Lemon leaf
Gavage doses of 25, 50 or 100 mg/kg/day of cinnamon bark Anise (star) Lemongrass
oil for 35 days decreased plasma glucose concentrations in KK- Basil (lemon) May chang
Ay diabetic mice (Ping et al 2010). Cinnamaldehyde, at oral Black seed Melissa
doses of 5, 10 or 20 mg/kg/day for 45 days, dose-dependently Cassia Myrtle
decreased plasma glucose concentrations in streptozotocin- Cinnamon bark Myrtle (aniseed)
diabetic male rats, and 20 mg/kg markedly increased plasma Dill Myrtle (honey)
insulin levels (Babu et al 2007). Wild Satureja khuzestanica Fennel (bitter) Myrtle (lemon)
oil (93.9% carvacrol) significantly reduced plasma glucose con- Fennel (Sweet) Tea tree (lemon-scented)
centrations in diabetic rats when given orally at 100 mg/kg/day Fenugreek Turmeric
for 21 days. It was thought that inhibition of liver phosphoenol- Geranium Verbena (lemon)
pyruvate carboxykinase may contribute to this action
(Shahsavari et al 2009). Other carvacrol-rich essential oils will
probably have similar effects. Plasma glucose concentrations
were significantly reduced in rats after gavage dosing with Oral ingestion of the essential oils listed in Box 7.2 is cau-
(1R)-(þ)-b-pulegone at 160 mg/kg/day for 28 days. The tioned in diabetic subjects whose blood glucose levels are being
authors suggested that this might be due to inactivation of controlled by orthodox drugs.
glucose-6-phosphatase (Mlck et al 1998). Apart from (þ)-
pulegone, it is interesting to note that most of the essential oils
exerting hypoglycemic activity here contain constituents that Summary
possess a carbonyl group, commonly as aldehydes or ketones.
Some phenols also seem to be active. Nevertheless, it must
be stated that these compounds do not necessarily share a com- • There is no hard evidence that any essential oil, by any route,
mon mechanism of action. exacerbates either hypertension or hypotension as used in
Hyperglycemic effects have also been seen. In normal rab- aromatherapy.
bits, 25 mg/kg im rosemary oil produced 20–55% increases in • Patients taking anticoagulant drugs, and other at risk
plasma glucose levels above those of control animals after individuals, should avoid oral administration of essential oils
60–120 minutes, and a 30% decrease in serum insulin levels that inhibit platelet aggregation.
(Al-Hader et al 1994). Anise oil significantly enhanced the • Emerging research indicates that some essential oils may be
absorption of glucose in rat jejunum. This action correlated with cytotoxic to erythrocytes, but there is currently insufficient
an increase in Naþ/Kþ ATPase activity (Kreydiyyeh et al 2003). information for specific contraindications.
Because anise oil and sweet fennel oil both affect glucose metab- • Experimental evidence suggests that some essential oils can
olism, we have included other (E)-anethole-rich essential oils in increase or decrease blood glucose concentrations. Oral
Box 7.2. We have not included essential oils that we recom- ingestion of these is cautioned in anyone taking medication to
mend should not be taken in oral doses. control blood sugar levels.

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