The alkaloids isolated from Viscum appear to be related to those found in the host plant.^3,⁴ For example, mistletoes growing on Solanaceae shrubs contain nicotine alkaloids like hyoscine, anabasine, and isopelletierine. Cardiac glycosides have been found in mistletoe growing on Nerium oleander; strychnine has been found in mistletoe growing on Strychnos species; and caffeine has been found in mistletoe growing on coffee plants.

Because pharmacologically active compounds appear to be concentrated within the mistletoe, different host trees providing diverse chemical constituents could be used for different therapeutic actions. Also of importance is the fact that the proteins/lectins are present only in aqueous extracts, indicating that their therapeutic activity would differ from that of the alcoholic/aqueous extracts. The alcoholic/aqueous extracts also demonstrate considerably less toxicity.

History and Folk Use

Mistletoe was held in great reverence by the Druids who, dressed in white robes, would search for the sacred plant. When some was discovered, a great ceremony would ensue, culminating in the mistletoe’s separation from the oak tree with a golden knife. The Druids believed that mistletoe protected them from all evil and that the oaks on which it was seen growing were to be respected because of the wonderful cures that the priests were able to produce with it.¹

Mistletoe’s use has been recorded in the Middle East, Africa, India, and Japan and it was mentioned as an anticancer drug by Pliny, Dioscorides, and Galen.³ In 1720, an English physician, Sir John Colbatch, extolled the virtues of Viscum in a pamphlet titled The Treatment of Epilepsy by Mistletoe. For many years, mistletoe was used in the treatment of a variety of nervous system disorders, including convulsions, delirium, hysteria, neuralgia, and nervous debility.^1,³ It has been used in naturopathic medicine in the treatment of hypertension and vascular disorders of the uterus, bladder, and intestines.

Probably because of Viscum’s potential toxicity, its use appears to have fallen into some disrepute shortly after Colbatch’s work. For many years it was used only in external preparations for the treatment of dermatitis. Then, in 1906, a study demonstrating Viscum’s hypotensive effect in animals and humans was published. This paper appears to have restored its medical prestige, initially in France and eventually throughout Europe.³

Pharmacology

V. album exhibits diverse pharmacologic actions. The herb and various extracts have demonstrated that it serves as

• A hypotensive

• A vasodilator

• A cardiac depressant

• A sedative

• An antispasmodic

• An immunostimulator

• An antineoplastic agent

Purified mistletoe lectins are, in general, not as active in experimental studies as are crude preparations.^11,¹² Presumably the crude preparations contain a number of compounds acting synergistically. It has also been proposed that alkaloid components are responsible for the maintenance of lectin structure and activity.⁵ During isolation and purification procedures, alkaloid linkages are cleaved from the lectins, resulting in a loss of specificity for target molecules. Unfermented Viscum preparations typically demonstrate greater direct cytotoxicity to tumor cells owing to higher concentrations of the viscotoxin mistletoe lectin I (ML I).¹³^–¹⁵

Cardiovascular Effects

Viscum has exhibited a variety of effects on the cardiovascular system.^3,¹⁶ In particular, Viscum has repeatedly demonstrated hypotensive action in animal studies. The mechanism of action for its hypotensive effect is still not entirely clear, and no recent investigations have been published. Viscum has been shown to inhibit the excitability of the vasomotor center in the medulla oblongata and to possess cholinomimetic activity.¹⁶

Viscum’s hypotensive activity may depend on the form in which the mistletoe is administered and the host tree from which it was collected. Studies indicate that aqueous extracts are more effective; the highest hypotensive activity was demonstrated by a macerate of leaves of mistletoe parasitizing on willow and gathered in January.¹⁶

Viscum’s nonprotein components—flavonoids, phenol carboxylic acids, phenylpropanes, and lignins—have been shown to possess hypotensive action. Alcoholic solutions (tinctures and fluid extracts) contain these compounds but not viscotoxins or lectins. As previously stated, however, aqueous extracts appear to be more effective.

Several Viscum preparations for hypertension are currently available in Europe. In fact, in Great Britain alone, more than 150 different mistletoe preparations are available.³ These preparations typically have small amounts of Viscum in combination with other botanicals with hypotensive action, such as garlic, Crataegus oxyacantha, and Tilia platyphyllos.

Antineoplastic and Immunostimulatory Effects

Viscum preparations have been used clinically in Europe for the treatment of cancer since 1926, when Iscador, a fermented product made from the crude pressed juice, was introduced as an immunotherapeutic agent for cancer. This work was carried out under the direction of Rudolph Steiner. Since that time, numerous studies have shown that Iscador and other Viscum preparations and components are effective antineoplastic and immunostimulatory agents.11–15,17–31

Iscador and other fermented Viscum preparations differ from nonfermented extracts in their greater effectiveness and their lower toxicity.¹⁷ Specifically, the major viscotoxin, ML I, is not found in Iscador.¹⁸ It is thought that fermentation transforms ML I to its A and B chains, which have important immunologic properties.¹³ The A chain has mitogenic effects, and the B chain stimulates macrophages and the release of lymphokines. In addition, there is a rapid decrease of lectins during fermentation.

The pharmacologic activity of Iscador has been shown to be due to its Viscum components rather than to other constituents, such as lactobacilli, which possess adjuvant activity. The lectins have clearly been demonstrated to be the Viscum components largely responsible for Iscador’s adjuvant activity. Although unfermented plant juice has demonstrated a tenfold greater cytotoxicity to tumor cells than Iscador in vitro, fermented Iscador contains a great number of substances that may act synergistically. In vivo studies in mice have demonstrated Iscador to have greater adjuvant activity than purified mistletoe lectin and to be without secondary toxic effects.^19,²⁰

Viscum’s adjuvant activity is demonstrable in both delayed-type hypersensitivity and antibody responses of mice to sheep red blood cells.^19,²⁰ Like other adjuvants (e.g., bacille Calmette-Guérin, levamisole, muramyl dipeptide, bacterial and yeast components, etc.), Iscador is most effective when it is administered near the tumor, although systemic administration has also yielded positive results. Upon local administration, an inflammatory process ensues that promotes white blood cell (WBC) infiltration and encapsulation of the tumor.

The nonspecific host defense factors stimulated by Viscum include the following: