Choline reduces immune inflammation and
suppresses oxidative stress providing important …

Asthma Relief
Throughout history, all of the great civilizations have dealt with asthma,
searching for knowledge of cause and cure.
By Will Block

L

egends have it that bronchial asthma has been treated for at least as long as 5000 years. I certainly know about its very recent history, because my brother had it as a child. As long as I can remember, at any moment he could be nearly crippled for lack of air when almost anything—dust, cigarette smoke, pollen, household cleaning agents, or even a passing whiff of perfume—could trigger a severe asthma attack in which his chest would clench up like a fist. He never went anywhere without his inhaler.

Asthma (from the Greek ásthma, “panting”) is a common chronic inflammatory disease of the airways (aka breathing tubes). Characterized by variable and recurring symptoms in which airflow is obstructed, asthma results in bronchial hyperreactivity or even bronchospasm. Its symptoms include wheezing, shortness of breath, chest tightness, and coughing. The prevalence of asthma has increased significantly since the 1970s. As of 2009, 300 million people were affected worldwide and there were 250,000 asthma deaths.

Throughout history, all of the great civilizations have dealt with this problem, searching for knowledge of cause and cure. While there has been some notable successes, nothing has completely relieved the misery.

Writings from ancient China, pharaonic Egypt, Mesopotamia, and the Greco-Roman period, as well as from the ancient Hebrews, reveal much about scientific thinking during the era designated as Early History. Although these records are open to interpretation, they may in fact contain the earliest descriptions of diagnoses and treatments of allergy and asthma. In studying documents from ancient China, Egypt, Greece, Rome, etc., it is hard to determine whether individuals were responsible for the novel medical observations and techniques described, or whether the new information represented accumulated knowledge handed down from generation to generation before recorded history. Probably it was a combination of both. For certain, medicine in these cultures was closely interwoven with religious practice, a misfortune that has frequently impeded scientific progress, and even reversed it.

From the Beginning: China and Ephedra

Ephedra sinica, known as ma huang in ancient China, is a remedy whose medicinal benefits were recognized and employed for millennia before its pharmacological properties were fully characterized. Nearly 5000 years ago the legendary Emperor Shennong, the father of Chinese herbal medicine, was said to have tasted every one of the herbs he cultivated to cure the sick … including ephedra. This herb, typically made into a tea, was shown to relieve bronchospasm. One thousand years later (about 2000 BC) one of its active components, ephedrine, was identified and found to produce vasoconstriction, reversing congestion, and inhibiting mucous secretion.

The Chinese eventually brought ephedra to Greece, from where it was introduced to other civilizations. Called Kim Iya, after the colors of the dragon (red and gold), the packaging of ephedra reflected immortality. This was Arabicized by pre-Islamic Arabs trading in silk with China as Kimiya, whence arose Al-Kimiya, and finally Al-chemy, which through the mind of Paracelsus—the great 16th century Renaissance physician, botanist, and alchemist—gave birth to Western pharmacology and, ultimately, a major part of the biomedical sciences as we know them.

Egypt’s Contribution to Asthma

The Ebers Papyrus (c. 1550 BC), a collection of medical works by early Egyptian physicians, revealed that respiration was considered to be the most vital function.1 Although the heart was recognized as the center of the circulatory system, Egyptian doctors also knew that the functioning of the heart was dependent upon respiration. Before the Middle Kingdom (2130–1550 BC), illnesses were thought to have natural causes. And treatment was believed to heal through the use of acquired skills. But after the Kingdom ended, religion—once a source of scientific inspiration and innovation—became rigid and formal.

Pantheism Stifled Inquiry

While Egyptian pantheism once spurred investigation, it eventually stifled it. The belief that illness was caused by supernatural intervention gained prevalence, and magic became more important than reason in the treatment of disease. It is not a wonder that politics played a role in the establishment of the “standards” of medical practice. According to custom, if a physician treated an illness in the manner approved by the committee and the patient died, the physician was blameless. If the physician deviated from the recommendations of the committee and the patient died, the physician was liable and could be executed.

On the cusp of the end of the Middle Kingdom, the Ebers Papyrus—believed to have been copied from earlier texts, perhaps dating as far back as 3400 BC—outlined nearly one thousand prescriptions remedies for asthma, hepatitis, bubonic plague, gonorrhea, scurvy, cataracts, epilepsy, hemorrhoids, etc. Asthma was considered to be a disorder or foulness of the ducts that were thought to distribute air and water to the organs, including the lungs. Consequently, physicians attempted to heal the lungs by dispelling the foulness. But the effectiveness of the remedies is difficult to determine, especially since many of the materia medica are unknown today. Most of the plant names did not survive to be included as part of a modern language. But a few, commonly prescribed for respiratory problems, did survive, and these are frankincense (from the species Boswellia, and shown scientifically to operate as an anti-inflammatory) yellow ochre (mechanism unknown), and grapes (the antioxidants in grape pomace are known to reduce oxidation and inflammation). Finally, the Ebers Papyrus also recommended the use of crude medical devices for improving inhalation in cases of restricted breathing. How effective any of these were is not known.

Asthma in the Greco-Roman Period

In ancient Greece a cult formed based upon the philosophy of the god of medicine and healing, Asclepius (c. 1200–900 BC). Trained by Chiron, the centaur who had taught the art of medicine to Achilles, Asclepius was a doctor of such extraordinary talent that he could raise the dead. Asclepius represents the healing aspect of the medical arts; his daughters are Hygieia (“Hygiene”), Iaso (“Medicine”), Aceso (“Healing”), Aglaea (“Healthy Glow”), and Panacea (“Universal Remedy”). The rod of Asclepius, a snake-entwined staff, remains a symbol of medicine today, although sometimes the caduceus, or staff with two snakes, is mistakenly used instead. Asclepius’ accomplishments eventually aroused the envy of the gods, who struck him dead, but later enshrined him in Mount Olympus.

Mesopotamian Art of Medicine

When historian Herodotus (c. 484 BC–425 BC) traveled to Babylonia, he dismissed their medicine based on his notion that there were no doctors there—but he was not correct. Mesopotamia had a long history of physicians. In fact, medical doctors were regulated by the Code of Hammurabi (c. 1760 BC), and many of their prescriptions, potions, and healing spells survive on cuneiform tablets. These tablets recorded symptoms of dyspnea. For example, “If a man’s lungs pant with his work,” and “When the breath of a man’s mouth is difficult.” An apparatus to ease breathing was also described. However, in the majority of medical texts written by successive generations of Sumerian, Babylonian, and Assyrian physicians, illnesses such as asthma were attributed to commission of a sin or possession by a demon, and cures were sought through repentance or magic. Free inquiry was bound up.

Hippocrates’ Ideals

Over centuries, learned Greeks began to separate medical fact from superstition. Born on the island of Kos (c. 460–377 BC), Hippocrates is generally regarded as the “Father of Medicine.” His teachings were based upon objective observation and deductive reasoning, and through his development of medicine as a profession, he became the most renowned and influential physician in western history. Indeed, Hippocrates’ ideals and principles were incorporated into the Hippocratic Oath, the ethical code that is still studied by medical students. Among his numerous contributions to medicine, Hippocrates described “panting,” from which the term asthma derives, and was among the first physicians to understand the relationship between the environment and respiratory ailments.

Asthma as Muscular Contraction

Greek and Greek-influenced physicians continued to use asthma to describe a degree of respiratory distress rather than a syndrome. In the 1st century BC, Roman encyclopedist Aulus Aurelius Cornelius Celsus—considered to be the first medical historian—described asthma as the inability to breathe without making noise and gasping. Aretaeus the Cappadocian (c. 2nd century AD), a Greek physician who practiced in Rome and Alexandria, is credited with the earliest documented description in existence in Western literature of what is now recognized as asthma.

Clarissimus Claudius Galenus (c. 129–199 AD), also known as Galen, lived and studied in the city of Pergamon, the center of the cult of Asclepius. Galen circumvented the Greco-Roman prohibition against dissection of the human body by operating on pigs and other animals and extrapolating his findings to human anatomy. Consequently, he was the first to discover that respiration was the result of muscular contraction, and not the expansion caused by breath warming the heart. He proved his hypothesis through the simple observation that the respiratory rate could be controlled consciously.

Although Pliny the Elder (Gaius Plinius Secundus) criticized the practices of the Greeks, his encyclopedic Historia Naturalis was greatly influenced by the Hellenic tradition. Importantly, Pliny acknowledged pollen, which he knew had a role in plant fertilization, as a source of respiratory distress. As a remedy for asthma, he recommended the use of ephedra (called anabis) in red wine.

The Hebrew Heritage

The early Hebrews, nomads during the course of their history, remained united by rigidly codifying their beliefs and culture. Some narratives suggest that at one time the Hebrews believed that catastrophes were due to supernatural interventions unrelated to God, and the phrasing of many psalms suggests that incantations were adapted into prayers. In addition, practices once associated with magic, such as the wearing of ritual apparel and the posting of small parchment scroll with ritual text, were redefined within the monotheistic religious and legal system of Judaism. Yet, as their culture developed, a significant distinction between magic and religion emerged. Disease, excluding “everyday” disorders, represented divine displeasure, a consequence of sin, which altered he approach to treatment. Epidemics were believed to be God’s wrath.

Jewish Tradition

Although Jewish tradition rejected any practice that might “harm” a corpse, including autopsy and embalming, it is clear from the Babylonian Talmud that the Jews had a relatively sophisticated comprehension of human anatomy and physiology for the time. The Talmud explicates, through its analysis of case law, much of what they understood about human health and illness. In Chapter IV, “Sickness and Their Treatments,” diseases of the lungs are described, including an observation on breathing: “The breathing of individual people differs, all according to the spirit for which God maketh a weight. Some people have a long (projecting) breath whereas others have a short breath; the latter, if he is possessed with [noisy catarrh (inflammation of the mucous membranes)].”

Another discourse of interest is on the use of asafetida, an odoriferous gum resin of oriental plants of the carrot family, genus Ferula. Commonly used in folk medicine as a prophylactic agent against an array of diseases, asafetida is mentioned in the Assyrian Herbal, a cuneiform tablet from 669–626 BC. It was believed that the digestion and elimination of this volatile oil through the lungs could prevent and treat bronchitis, whooping cough, and asthma. The Talmud cites it as a remedy for asthma. Recently, it has been shown to help fight the influenza A virus.2

Medicine in India

Embracing the Ayurvedic medicine tradition of India, the Susruta Samhita (dating from the 3rd or 4th century AD) contains a lecture that described the anatomy and dissection of the human body. Indian physicians believed that “winds” were essential to the functioning of the body and that these winds, of which there were five, were inhaled through the breathing process.

Indian pharmacology was ahead of its time, the recognition of which resulted in the exportation of medicinal plants and therapies to Greece and Egypt soon after Alexander’s invasion. Two herbs are recommended in the Susruta Samhita for their relaxant properties: Saussurea lappa (kuth root)3 and Nardostachys jatamansi (Datura or thorn-apple),4 from which stramonium was extracted. The great Materia Medica of Dioscorides (c. 40–90 AD) is deeply indebted to Indian herbal investigations. Following the British army’s 19th century incursion into India, the practice of smoking stramonium was introduced to the West as a treatment for asthma, substituting the more temperate genus Datura stramonii for the tropical genus Datura ferox.

Arabic Medicine

Born near Tehran, Rhazes, (c. 865–932 AD) was a Persian medical writer who first described seasonal allergic rhinitis, or what was then referred to as rose fever. Avicenna (c. 980–1037 AD) was lauded as the “Prince of Physicians” and in his most famous work al-Quanun fi al-Tibb (The Canon of Medicine) he identified three stages of the physician’s visit: examination, consultation, and prescription of the treatment agents. His medical textbook was required reading throughout both the Islamic and Christian worlds for more than five hundred years after his death.

Serving as physician to the legendary sultan Saladin, Maimonides (1135–1204 AD) attended the Muslim leader’s son who suffered from chronic asthma. In his Treatise on Asthma, he suggests comprehensive treatment measures including rest, good personal hygiene, environmental hygiene, equanimity, and the avoidance of opium(!). To prevent asthma attacks, Maimonides recommended a diet free of nuts, fowl, milk, and legumes.

Salerno, a coastal town in Italy, had been famous for centuries for its numerous physicians. A prominent medical school was established in Salerno, where Regimen Sanitatis Salernitanum (The Salerno Book of Health) written in verse form, strangely enough. It discussed “The matter that causeth Asma.”

Pre-Columbian Medicine in America

Before the arrival of Columbus, the early peoples of South America and Mexico utilized natural resources as cures including the dried root of the Brazilian shrub Cephaelis ipecacuanha (aka ipecac), which possesses expectorant properties, and balsam, used as a component of some cough medicines even today.

The herbs atochietl (possibly Pennyroyal) and tzompilihuizxihuitl (possibly Galium sp., try to pronounce it) were pungent inhalants used to clear the head. The ancient Americans also used ephedra. Cocaine, the principal ingredient of the dried leaf Erthroxylon coca, was another Incan herbal remedy and was later used in both the United States and Europe to treat rhinitis and asthma.

Current and Future Asthma Treatment

On the doorstep of the 21st century, many believe that with the advent of inhaled corticosteroids, control of asthma has achieved what the medicines of the past have been unable to do. Indeed, current allergy and immunology texts dictate that the wealth of important new information takes precedence over the historical perspective. This is unfortunate. The historical perspective is invaluable and must not be lost. Furthermore, the current picture is not so rosy. Therapeutic interventions may reduce airway inflammation and relieve symptoms, but they are also associated with potential side effects that limit their usefulness.

New Choline Study for Asthma

With this is mind, a new study was undertaken to assess the effect of choline on immune inflammation and bronchial hyperreactivity in asthma subjects.5 Choline is an essential nutrient with a Daily Value of 550 mg for men, and 425 mg for women. However, these figures have been shown to be inadequate for older individuals (see “Are You Getting Enough Choline” in the August 2007 issue).

In the study, 76 asthma patents (between 15 and 45 years of age) were recruited and treated with either a choline supplement (1500 mg of choline chloride,* twice daily) or standard pharmacotherapy for 6 months. Following that, the subjects were evaluated by clinical, immunologic, and biochemical parameters.


* Choline chloride is known to be a bioavailable form of choline, as is choline citrate.


Treatment with choline showed significant reduction in symptom/drug score and improvement in the provocative concentration of methacholine causing a 20% fall in forced expiratory volume (PC20 FEV1) compared to baseline or standard pharmacotherapy. At the same time, choline therapy significantly reduced interleukin (IL)-4, IL-5 and tumor necrosis factor-alpha (TNF-α) levels as compared to baseline or standard pharmacotherapy after 6 months. Each of these is an inflammatory marker.

Blood eosinophil count and total immunoglobulin E levels were reduced in both the treatment groups. An elevated blood eosinophil count is associated with a number of reactive conditions, and sustained high levels for longer than six months, can cause damage to end organs such as the heart, lungs, skin, joints and the nervous system. IgE is reflective of immune system respond and are associated with allergy hypersensitivity.

Also, cysteinyl leukotriene and leukotriene B4 were suppressed significantly by choline. Leukotrienes contribute to the pathophysiology of asthma, causing or potentiating, 1) airflow obstruction, 2) increased secretion of mucus, 3) mucosal accumulation, 4) bronchoconstriction, and 5) infiltration of inflammatory cells in the airway wall. Suppression of leukotrienes was accompanied by decreased 8-isoprostanes, a biomarker for oxidative stress after choline treatment.

Choline for Immune Enhancement

This study breaks new ground, and is the first report showing the effect of choline in reducing IL-5 as well as peripheral blood eosinophil counts in asthma patients. Taking this all together, choline modulates immune inflammation and suppresses oxidative stress in asthma patients, and it can be used as an adjunct therapy for asthma patients. This is especially important in those for whom additional anti-inflammatory treatment is required and who fail to respond adequately to inhaled corticosteroids therapy. Because controlled clinical trials have demonstrated that inhaled corticosteroids are associated with systemic side effects, new approaches are required which can control immune inflammation with no or minimum side effects, and that may include choline.

Choline is inexpensive and quite safe to use, and at the levels used (3 g/day) is below the level of tolerable upper intake level set by the Institute of Medicine of the National Academy of Sciences. Moreover, although choline’s mechanisms of activity are not entirely clear, because of its precursor role for making acetylcholine (the universal neurotransmitter in muscles) in the body, in all likelihood it does something that corticosteroids can’t do. It may actually strengthens muscles and helps prevents respiratory contraction, while it enhances immune system activity. That’s a great deal.

References

  1. Cserháti E. The history of bronchial asthma from the ancient times till the Middle Ages. Acta Physiol Hung 2004;91(3-4):243-61.
  2. Lee CL, Chiang LC, Cheng LH, Liaw CC, Abd El-Razek MH, Chang FR, Wu YC. Influenza A (H(1)N(1)) antiviral and cytotoxic agents from Ferula assa-foetida. J Nat Prod 2009 Sep;72(9):1568-72.
  3. Raghavan P, Nagendra AS, Dutta NK. Total alkaloids of Saussurea lappa in treatment of bronchial asthma. An assessment of its therapeutic value by clinical and ventilatory function studies. J Postgrad Med 1962 Oct;8:158-69.
  4. Gupta SS, Patel CB, Mathur VS. Effect of Nardostachys jatamansi fumes and aerosols in histamine-induced bronchial asthma in guinea pigs. J Indian Med Assoc 1961 Sep 1;37:223-5.
  5. Mehta AK, Singh BP, Arora N, Gaur SN. Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma. Immunobiology 2010 Jul;215(7):527-34.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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