Docetaxel

Rockwell S, Liu Y, Higgins S. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res Treat 2005;90(3):233-239.

This in vitro study used common mouse breast cancer cell lines to see if black cohosh extracts altered the response of cancer cells to radiation and to four drugs commonly used in cancer therapy. Black cohosh extracts increased the cytotoxicity of doxorubicin and docetaxel. However, it decreased the cytotoxicity of cisplatin. It did not alter the effects of radiation or an analog of cyclophosphamide.

Commentary: One of the more challenging situations for postmenopausal breast cancer patients is the management of their menopause symptoms without hormone replacement therapy, especially hot flashes and nightsweats. Previous reports/studies have concluded that black cohosh did not increase breast cancer cell division and actually markedly inhibits the proliferation rate of estrogen receptor positive breast cancer cells. (1) Black cohosh has also been shown to not have estrogenic activity and does not promote breast cancer cell growth in another study. (2) To my knowledge, there has not been one published study in vitro, human or animal that cites a negative effect on breast cancer cells or causing breast cancer. This latest study is yet one more encouraging step in the assessment of the safety of black cohosh for menopausal breast cancer patients. It is one of our most important tools in alleviating their menopausal symptoms. According to this study, black cohosh should be avoided if patients are on a cisplatin regimen, most likely utilized in ovarian cancer patients.

Migraine Headaches in Women

Women account for about three-quarters of the 28 million Americans who experience migraine headaches. Attacks can begin at any age, but they typically start during childhood or adolescence when they are pretty equal in boys and girls. By early adolescence though, the prevalence becomes more dominant in women. This prevalence of migraines peaks in women in their early forties, and then declines steadily as we age, but may not resolve completely. Migraines tend to reduce in frequency in postmenopausal women, with estrogen levels decreasing significantly and also stabilizing without monthly fluctuations.

The process of migraines begins in the nervous system. Rather than a vascular or muscular disorder, as we thought in the past, migraines are really a neurological condition. It begins when the sensitive nervous system of a migraine sufferer is faced with an environment that can reduce their migraine threshold. These risk and trigger factors include hormonal changes, alcohol consumption, skipping meals, sleep deprivation, medications, and other stressors. Under these circumstances, the neurochemical balance of the nervous system changes, and prodromal symptoms can occur. If this state progresses, the migraine threshold is crossed, and the "migraine generator" area of the brainstem is now activated. A wave-like effect occurs across the surface of the brain, nerve cells and selected nerve branches and the vascular structures they supply are activated. As the branches of the involved nerves are activated, neuropeptides are released from the nerve. These then produce an inflammation of small arteries which stimulate blood platelet "stickiness" and serotonin release, potentiating the migraine process. Nerve impulses are transmitted back to the brainstem and as the process continues, brainstem reflexes are activated that produce the migraine-related symptoms, ex/ nausea, vomiting and photophobia. Pain fiber activation can also result in nasal congestion and pain in the sinus cavities.

Migraines are a complex neurologic process, and headaches are only one of many symptoms that can present during an attack. For women, proper management of migraines may also need to include the consideration of their hormonal situation. Migraines can be related in timing to the menstrual cycle, when there are fluctuations in hormones that then affect the brain chemistry and vasculature. Some women may find their migraines are worse, before, or during or after their menses. This then may require altering or balancing their hormonal environment in order to get the best results. Some women will find that their migraines worsen when taking oral contraceptives. Fortunately, the majority experience no change or even improvement in their headache pattern with oral contraceptives. Migraine management during pregnancy can be complicated. Although many women experience relief from headaches during pregnancy, others find that migraine symptoms stay the same or worsen. Finding effective solutions for migraine pain during pregnancy, whether with drug medications, or natural substances is problematic due to potential harm to the pregnancy. As with menstrual migraines, migraines at perimenopause may require altering or balancing or stabilizing of the hormonal environment.

Butterbur, specifically the extract of the rhizome of the plant, when standardized to contain 15% petasins, reduces spontaneous activity and spasms in the smooth muscle of the vascular walls. It also reduces leukotrienes and thus provides an anti-inflammatory effect as well. Historically, Petasites has been used for its analgesic effects. Numerous research reports have demonstrated that butterbur reduces the frequency and intensity of migraine attacks. (3) More recently, a randomized, double-blind, placebo-controlled clinical trial for migraine prevention was conducted on 229 migraine patients. Petasites extract was found to be safe and effective in reducing the frequency of migraine episodes, the number of days of migraine per month, and the intensity of the headache itself. (4)

Ginger is one of our best anti-inflammatory plants, as well as able to reduce blood platelet stickiness. Anecdotal reports suggest that ginger taken daily can reduce the frequency of migraines as well as reduce the intensity. The best known herb for the prevention of migraines is feverfew.

Feverfew is a member of the daisy family and is derived from the Latin for "chase away fevers." Feverfew is rich in compounds known as sesquiterpene lactones. The most predominant of these is parthenolide. Feverfew leaf inhibits platelet stickiness and histamine release, as well as regulating serotonin release from the platelets. This is what is believed to reduce the severity, duration and frequency of migraine headaches and leads to an improvement in blood vessel tone. Feverfew also inhibits prostaglandin synthesis and the release of arachadonic acid, which explains its further anti-inflammatory effects. The initial survey on feverfew and migraines was done with 270 migraine sufferers who had eaten feverfew daily. They found that 70% of those individuals had a decrease in the frequency and/or intensity of their attacks. (5) Several clinical studies have been done to explore the treatment and prevention effects of feverfew with most showing the ability to reduce frequency, duration and intensity. (6) Visual disturbances, nausea and vomiting associated with the attacks may also be reduced with feverfew.

Riboflavin appears to have an important role in reducing the frequency of migraines. Riboflavin has the potential of increasing energy efficiency within the cell. It is thought that this ability can then bring about stability of cerebral blood vessels and thereby reduce the frequency and intensity of migraines. Forty-nine migraine patients were treated with 400 mg per day of riboflavin for 3 months. Those in the migraine group had a 68% reduction in the migraine severity score. (7)

Low magnesium levels may also play a significant role in headaches. Low magnesium levels have been detected in sufferers of both migraine and tension headaches. (8-11) A magnesium deficiency may be the precursor for events that can lead to a migraine attack or tension headache. In one study, patients suffering from recurrent migraines had a 41% reduction in frequency by week nine when taking magnesium daily. (12) The number of days with pain also decreased in the magnesium group as well as a decreased need for pain medications. It may be that only those who have low magnesium levels in the tissue or blood, may benefit from taking magnesium.

5-hydroxytryptophan (5-HTP) also has an important role in the migraine process, by modulating serotonin levels and increasing endorphin levels. Several studies have compared 5-HTP with a pharmaceutical prescription. In one of the largest clinical trials, 124 patients received either 5-HTP or methysergide for six months (13); 71% of the patients who were taking 5-HTP demonstrated significant improvement in frequency and number of severe attacks, which was the same as the effect achieved with the prescription medication. Two other studies demonstrated that 5-HTP was superior to the pharmaceutical prescription. (14, 15) For those individuals who have headaches that are also accompanied by sleep disorders, 5-HTP is especially appropriate.

It may appear as contradictory that we use 5-HTP, known as a natural method of increasing serotonin levels, and that increased serotonin release in the brain is a potentiator of the migraine process. The class of migraine medications called triptans have revolutionized migraine treatment. Triptans are serotonin-receptor 1B and 1D agonists. The therapeutic action of these agents is attributed to their selective activity on serotonin receptors on intracranial blood vessels and on the trigeminal nerve. Activation of these receptors will then cause vasoconstriction of intracranial vessels that are abnormally dilated and inhibit neurogenic inflammation. As a result, the headache is relieved as well as associated symptoms such as nausea, photophobia and phonophobia. The key is probably the effect at the level of the serotonin receptor and perhaps the constricting effect of activating these receptors overrides any other mechanism.

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Remember that the holistic approach to improving migraines is to address hormonal imbalances and influences. Reduce or avoid common triggers: dietary amines (chocolate, cheese, beer, wine). Reduce or avoid the most common foods that induce migraines (dairy, wheat, chocolate, eggs, fish, coffee, nuts), and known or suspected individual food allergens. Consider nutrient deficiencies, stress, skeletal misalignments and muscle tension. As always, eat a whole foods diet free of preservatives, white sugar, white flour and fried foods.

References

1. Nesselhut T, Schellhase C, Dietrich R, Kuhn W. Examination of the proliferative potential of phytopharmaceuticals with estrogen-mimicking acting in breast carcinoma. Arch Gynecol Obstet 1993;254:817-818.

2. Lupu R, Mehmi I, Atlas E, et al. Black cohosh, a menopausal remedy, does not have estrogenic activity and does not promote breast cancer cell growth. Int J Oncol 2003;23(5):1407-1412.

3. Gruia F. Biological treatment of pain. Results of a doctors' practice study with a phytopharmaceutical. Erfarungsheilkunde 1986;35:396-401. (article in German)

4. Lipton R, Gobel H, Wilks K, Mauskop A. Efficacy of Petasites (an extract from Petasites rhizome) 50 and 75 mg for prophylaxis of migraine: results of a randomized, double-blind, placebo-controlled study. Neurology 2002;58:A472.

5. Johnson E, et al. Efficacy of feverfew as prophylactic treatment of migraine. Br Med J 1985;291:569-573.

6. Volger B, Pittler M, Ernst E. Feverfew as a preventive treatment for migraine: a systematic review. Cephalagia 1998;18:704-708.

7. Schoenen J, Lenaerts M, Bastings E. High dose riboflavin as a prophylactic treatment of migraine: Results of an open pilot study. Cephalalgia 1994;14:328-329.

8. Mazzotta G, et al. Electromyographical ischemic test and intracellular and extracellular magnesium concentration in migraine and tension-type headache patients. Headache 1996:357-361.

9. Swanson D. Migraine and magnesium: eleven neglected connections. Perspect Biol Med 1988;31:526-527.

10. Ramadan N, et al. Low brain magnesium in migraine. Headache 1989;29:590-593.

11. Gallai V, et al. Magnesium content of mononuclear blood cells in migraine patients. Headache 1994;34:160-165.

12. Peikert A, et al. Prophylaxis of migraine with oral magnesium: Results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalagia 1996;16:257-263.

13. Titus F, et al. 5-hydroxytryptophan versus methysergide in the prophylaxis of migraine: Randomized clinical trial. Eur Neurol 1986;25:327-329.

14. Bono G, et al. Serotonin precursors in migraine prophylaxis. Adv Neurol 1982;33:357-363.

15. Maissen C, Ludin H. Comparison of the effect of 5-hydroxytryptophan and propranolol in the interval treatment of migraine. Med Wochenschr 1991;121:1585-1590.

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