SCIENTIFIC INFORMATION Reproduced from www.pharmaceutical-int.com/article.asp?pubID=13&catID=631&artID=1058 INNOVATIVE APPLICATIONS OF HOPS (Humulus lupulus L.) FOR RELIEF OF MENOPAUSE RELATED SYMPTOMS Professor Denis.De Keukeleire University of Gent, Belgium Menopause is best described as the period in which a woman, as a result of a decreased oestrogen and progesterone production by the ovaries, turns from fertile into infertile condition. Women are confronted with this on average when they are around 50 years old. The so-called ‘transition’ – which is not a disease,
and to balance the increased risk of breast cancer,
but a natural phenomenon – lasts a few years.
which appears after only 2 years of therapy, against
Menopause can be divided in two stages: the peri-
the decreased risk of uterus cancer. The present
menopause and the post-menopause. During the
strategy of doctors may also be influenced by an
peri-menopause, women feel the first menopausal
American study, which has just been published in
symptoms, one of these are hot flushes, caused by
the medical journal valued most highly in the world,
unusual fluctuations in the hormone levels and
New England Journal of Medicine (5). A significant
accompanied by very irregular menstruation cycles.
rise in the cardiovascular disease risk was found
The post-menopause starts as soon as 12 months
during the 1st year of combination HRT. In the past,
have gone by since the last menstruation. For many
it was believed that HRT would protect women from
women, the transitional process involves a range ofsymptoms and discomforts: hot flushes and wavesof heat, sleeping disturbances, structural changes inbladder and vagina, strongly reduced libido, higher
impression, both on doctors and on patients, not
cardiovascular disease risks, decrease of bone
only in the United States, but worldwide (in our
density (osteoporosis or bone decalcification) with
country as well). The market for HRT products in
an increased risk of hip, leg and arm fractures.
the United States and in England has collapsed andit may be stated that HRT at this moment can only
Hormone replacement therapy under debate
be supported in very serious cases of menopausalcomplaints and osteoporosis among women with a
Medicalisation of menopause is a ‘hot’ item. Women
limited cancer risk. There is no more room for long
can expect to live for about 30 years after
term HRT, especially not when the treatment is
menopause. For a healthy, active and fulfilling post-
menopausal life, women need to make some efforts,whether by adapting their lifestyles, of which
Control of menopausal symptoms through
nutrition is a part, or by taking extra nutritional
oestrogenic plants
supplements and/or treatment with medication. An
adequate means for fighting the symptoms involved
In these severe health problems, nature can be of
in menopause is the well-known hormone
great help. The fact is that many plants contain so-
replacement therapy (HRT), in which women, in
called phyto-oestrogens (‘phyto’ means ‘plant
general orally, take a small dose of semi-synthetic
derived’); these are non-steroidal constituents,
hormones. On July 9, 2002 however, the American
which bear a structural resemblance to endogenous
Women’s Health Initiative (WHI), a large-scale,
oestrogens and which imitate their activity. Phyto-
long-term study (8,5 years) on the advantages and
oestrogens are able to fill up the hormone deficiency
disadvantages of HRT, in which 16,608 menopausal
in menopausal women in a natural way and to
women (50-79 years old) were involved, was
relieve menopausal symptoms (6). An important
broken off after 5.2 years (1), as the risks of
additional advantage is that, since the hormonal
invasive breast cancer, arterial rupture, stroke and
activity of phyto-oestrogens is much weaker than
lung embolism were raised significantly. The
that of the hormones of the body itself, the
advantages in relation to a reduced risk of hip
influence on hormone dependent cancers, such as
fractures and cancers of the large intestine and of
breast and uterus cancers, is weakened.
the uterus were outweighed by this (2). Moreover,
on December 11, 2002, the federal US government
Plants, which are rich in oestrogens, normally do
published its two-yearly Report on Carcinogens, in
not occur as such in western nutrition these days.
which the steroidal oestrogens, used in HRT and in
As a result, they can only be ingested as derived
oral contraceptives, were added as a group to the
products or nutritional supplements. It is apparent
official list of ‘known human carcinogens’ (3). In the
that menopausal women are massively switching
report, the increased cancer risks, especially breast
from HRT to alternative preparations, based on
natural phyto-oestrogens with a suitable safety
profile. Numerous clinical studies support the
Very recently, the results of the British Million
activity of phyto-oestrogens in relation to
Women Study, in which 1 million menopausal
menopausal symptoms, while there are also strong
women were involved, were published in the leading
epidemiological indications of a causal connection
magazine Lancet (4). The conclusion of this largest
between a typically Asian diet, in which oestrogen
study ever on the relation between HRT and breast
rich soy plays an important role, and the limited
cancer, was that HRT (combination of oestrogens
incidence of hormone-dependent cancers and
and progestins) doubled the risk of breast cancer,
menopausal complaints among Asian women.
versus a 30% rise for HRT with only oestrogens. In
the last 10 years, 20,000 extra cases of breast
Only a limited number of oestrogenic plants exist
cancer were diagnosed among British women
and they are used regularly in the treatment of
between 50 and 64 years of age as a result of long-
menopausal symptoms. In Belgium, it seems that
term application of HRT. Doctors are advised to
some 20 phyto-oestrogenic plants are commercially
discuss HRT with their patients on a yearly basis
available, derived from soy (Glycine max L.,
isoflavones, such as genistein and daidzein), red
AUTHOR BIOGRAPHY
clover (Trifolium pratense L., coumestrol as active
phyto-oestrogen), black cohosh (CimicifugaProf. Dr. Denis De racemosa L.), chaste tree or chaste berry (VitexKeukeleire, agnus-castus L.) and yam (Dioscorea villosa L.)
Hops (Humulus lupulus L.)
In 1999, the research team of Prof. Dr. Denis De
Original applications of hops
Keukeleire of the Faculty of Pharmaceutical Sciences
in the fight against
at the University of Ghent, published for the first
menopausal symptoms
time that hops contain the strongest natural phyto-
oestrogen, that is 8-prenylnaringenine, also called
hopein, which belongs to the class of polyphenols,
prenylflavonoids (7). This revealing and intriguing
finding has meanwhile been confirmed by 5
independent research teams in Germany, England
and Japan (8). What is more, a Japanese research
team has discovered that hopein has a potent effect
on bone decalcification (9), while a French research
centre has shown that hops strongly reduce hot
flushes (10). Hopein seems to be a ‘miracle
molecule’ for menopausal women. Moreover, hops
contain another substance, xanthohumol, which,
just like hopein, belongs to the prenylflavonoid
group, but, in contrast to hopein, does not show any
oestrogenic activity. At the German Centre for
Cancer Research in Heidelberg, the anti-cancer
property of xanthohumol was studied in detail as
part of an extensive study, in which more than
2,000 vegetable compounds were examined by
some 20 anti-cancer tests. Only xanthohumol was
active in all tests, which illustrates the exceptional
value of this compound of hops. Xanthohumol
shows a remarkably broad spectrum of inhibition
mechanisms at the initiation, promotion and
The food supplements derived from hops available
on the market at this moment are focused on the
tranquilizing (sedative) effect of the plant.
Generally, these are combinations with other plants,
such as valerian and lemon balm. Some 1% of the
world production of hops (99% is intended for
breweries) is used as such or as a simple watery-
References 1. Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Journal of the American Medical Association 288:321-333 (2002). S. Ramsay. Trial of HRT to prevent CHD halted early because of
increased harm. Lancet360:146-146 (2002). 2. The American College of Obstetricians and Gynecologists (ACOG; www.acog.org), zie:
http://www.acog.org/from_home/publications/press_releases/nr08-30-02.cfm. 3. The Report on Carcinogens, 10th Edition, zie: http://ntp-server.niehs.nih.gov. 4. The American College of Obstetricians and Gynaecologists. Use of botanicals for management of menopausal symptoms, zie:
http://www.acog.org/from_home/publications/misc/pb028.htm. 5. V. Beral and the Million Women Study collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet362:419-427 (2003) 6. H. N. Hodis et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. New England Journal of Medicine 349:535-545 (2003). 7. S. R. Milligan, J. C. Kalita, A. Heyerick, H. Rong, L. De Cooman, D. De Keukeleire. Identification of a potent phytoestrogen in hops
(Humulus lupulus L.) and beer. Journal of Clinical Endocrinology and Metabolism84:2249-2252 (1999). Vervolgpublicaties: R. S. Milligan, J. C. Kalita, V. Pocock, V. Van de Kauter, J. F. Stevens, M. L. Deinzer, H. Rong, D. De Keukeleire. The endocrine activities of 8-prenylnaringenin
and related hop (Humulus lupulus L.) flavonoids. Journal of Clinical Endocrinology and Metabolism 85:4912-4915 (2000). S. R. Milligan, J. C. Kalita, V. Pocock, A. Heyerick, L. De Cooman, H. Rong, D. De Keukeleire. Oestrogenic activity of the hop phyto-oestrogen, 8-
prenylnaringenin. Reproduction123: 235-242 (2002). 8. N. G. Coldham, M. J. Sauer. Food and Chemical Toxicology 39:1211-1224 (2001). S. Gester et al. Tetrahedron 57:1015-1018 (2001). O.
Zierau et al. Planta Medica 68:449-451 (2002). O. Schaefer et al. Journal of Steroid Biochemistry and Molecular Biology 84:359-360 (2003).
T. Takamura-Enya et al. Food and Chemical Toxicology 41:543-550 (2003). 9. M. Miyamoto, Y. Matsushita, A. Kikokawa, C. Fukuda, Y. Iijima, M. Sugano, T. Akiyama. Estrogenic effects of 8-isopentenylnaringenin on bone metabolism, Planta Medica 64: 769-769 (1998). 10. P. Goetz, Traitement des bouffées de chaleur par insuffisance ovarienne par l’extrait de houblon (Humulus lupulus) Revue de Phytothérapie Pratique (4):13-15 (1990) 11. C. Gerhauser, A. Alt, E. Heiss, A. Gamal-Eldeen, K. Klimo, J. Knauft, I. Neumann, H. R. Scherf, N. Frank, H. Bartsch, H. Becker. Cancer chemopreventive activity of xanthohumol, a natural product derived from hop. Molecular Cancer Therapeutics 1: 959-969 (2002).
It is a paradox of the work of Artificial Intelligence that in order to grant con-sciousness to machines, the engineers first labour to subtract it from humans, asthey work to foist upon philosophers a caricature of consciousness in the digitalswitches of weights and gates in neural nets. As the caricature goes into publiccirculation with the help of the media, it becomes an acceptable counter
MATERIAL SAFETY DATA SHEET 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE AND OF THE COMPANY/UNDERTAKING Product name(s) Recommended uses and restrictions Raw, commingled bovine milk must be used. 24 hour Emergency Phone # CHEMTREC 1-800-424-9300 2. HAZARDS IDENTIFICATION According to Regulation (EC) No1272/2008 SNAP Device This substance is not classified as dangero