Rutin for the Capillaries

by JAMES F. COUCH

THE PRINCIPAL effect of rutin when taken into the body is to restore the strength of the capillary walls when they become weakened. Rutin is a new, cheap, nonpoisonous drug that comes from buckwheat, tobacco, yellow pansies, and at least 35 other plants. Extensive clinical studies of its use in various disease conditions associated with hemorrhage or weak capillaries have demonstrated the value of rutin in medicine.

In 1936 a Hungarian biochemist, A. Szent-Gyorgyi, announced that he had accidentally discovered a substance that would restore weakened capillaries to normal. The substance, which he called vitamin P, could be obtained from citrus fruits and red peppers. It was distinct from vitamin C, which had previously been thought to have this strengthening action. Szent-Gyorgyi and his co-workers began a search for the new factor and soon announced that it was a glucoside termed hesperidin, a well-known constitutent of citrus fruits that had been discovered more than a century previously. Further research, however, indicated that the vitamin P activity of hesperidin was due to some other substance, present as an impurity in the original crude crystals. Continuing the search, they Prepared a concentrate that contained eriodictin (eriodictyol glucoside), a compound closely related to hesperidin but more soluble in water.

Clinical studies showed this material to be active against increased capillary fragility, but again it was found that the activity was due to some other substance mixed with the crude eriodictin concentrate. Evidence was obtained that a related substance, long known as quercitrin, was present in these extracts. It was subjected to study on guinea pigs and appeared to be inactive. Szent-Gyorgyi concluded from all his experiments that vitamin C ( ascorbic acid) is needed to activate vitamin P and that when vitamin C is given simultaneously, both hesperidin and eriodictin restore weakened capillaries to normal.

Meanwhile, certain adverse reports were published, but favorable results were reported by scientists in Scotland and England. Many other fruits were studied and several gave evidence that they contained the capillary factor. From the contradictory accounts in the scientific journals, it became clear that the content of active material in the natural products is variable and that some samples may even be devoid of activity. Possibly the active factor is more concentrated at certain stages of growth, or the chemical processes used in concentrating the experimental fruit extracts may damage or destroy it.

The search for the missing factor was continued in various places. A. L. Bachrach and his co-workers in England have contributed extensive chemical studies on citrin and related substances. A. J. Lorenz and L. J. Arnold in California have reported a method of analysis for vitamin P. W. P. Wilson, also of California, has developed a colorimetric method for estimating flavonols. R. H. Higby, in the same laboratory, has studied a soluble form of hesperidin, the chalcone, which he thought might be the active form of the vitamin.

From what was known of the chemistry of the active material, it was evident that this elusive factor was most likely to be of a flavonol structure. The chemical structures of the compounds are similar.

The differences between the flavanone and flavonol structures are slight, but important. The flavonols contain an extra double bond and an hydroxl (OH) group, which are absent in the flavanones. Because these structures usually confer greater physiological as well as chemical activity on the compounds that contain them, we can expect that the flavonols would be more potent in the body than the flavanones.

The structure of rutin is the same as that of quercitrin, except that the sugar portion of the molecule is composed of glucose and rhamnose, whereas in quercitrin the glucose is absent and rhamnose alone is present. We reasoned, therefore, that rutin should possess a vitamin P action and might be the long-sought factor. Clinical testing for 4 years has substantiated the conclusion, and rutin is now established as a remedy for weakened capillaries.

Rutin can be prepared in a highly purified condition as a light-yellow, tasteless powder of definite chemical composition. Under the microscope, it appears in characteristic tufts of crystals. It is not toxic. Extensive feedings of large doses to laboratory animals over long periods as well as administration to human patients for many months have shown no deleterious effects.

Thirty-eight species of common plants are known to contain rutin. Among them are buckwheat (Fagopyrum esculentum), yellow pansy (Viola tricolor), elder (Sambucus canadensis), forsythia (Forsythia splendens and fortunei), hydrangea (Hydrangea paniculata), and tobacco (Nicotiana tabacum).

At the Eastern Regional Research Laboratory, rutin was first prepared from flue-cured tobacco of high quality. The yield was not large, averaging about 0.4 percent, at a material cost of $135 to $150 a pound for the drug. Other types of tobacco, especially the air-cured varieties, were never found to contain more than minute traces. Because of the expense involved in preparing rutin from tobacco, a search was begun to find a cheaper source. Many plants were examined in the laboratory. Several of these, like elder blossoms and leaves, pansy flowers, and white hydrangea flowers, contained enough rutin to be given consideration as possible though somewhat expensive sources.

When buckwheat plants became available, a sample was collected and brought to our laboratory. Analysis showed that it was the most promising plant examined up to then. Further research, including studies of the rutin content of buckwheat at different stages of growth and under varying conditions of handling and storage, disclosed that buckwheat gave a much higher yield (3 to 5 percent) and was so cheap that the material cost of rutin could be reduced to $1.10 a pound. Ten dollars worth of green buckwheat will furnish as much rutin as $ 1,000 worth of tobacco. Besides, buckwheat is a quick crop. In 25 to 30 days after sprouting, the Plant contains the highest percentage of rutin, but the greatest yield per acre is obtained 10 to 14 days later, advantage being taken of the extra growth of the plant during that period. This short period of about 40 days from planting to harvest makes it possible to obtain three crops a year from one plot of ground, an economic feature of some importance.