Transdermal Histamine in Multiple Sclerosis

Part Two: A Proposed Theoretical Basis for Its Use

George Gillson, MD, PhD, Jonathan V. Wright, MD, Elaine DeLack, RN, and George Ballasiotes, BSc, Pharm

Abstract
This paper is the companion to an earlier publication, which discussed preliminary results of transdermal histamine use for ameliorating symptoms of both relapsing-remitting and progressive multiple sclerosis (MS). Here we include preliminary findings on the impairments of digestion and assimilation in MS patients seen in a private clinic. Although only a small number of patients was surveyed, an association was found between impaired gastric acid production, impaired protein hydrolysis, and subnormal plasma histidine levels in patients with MS. Impaired digestion might, therefore, impair the ability of MS patients to synthesize histamine. This paper discusses how impairment of histamine synthesis might lead to symptoms of MS, and conversely how exogenously administered histamine might alleviate symptoms. Various mechanisms of action are suggested, including: enhanced gastric acid and pancreatic enzyme secretion, augmentation of subnormal cerebral tissue levels of histamine, improved electrical function of demyelinated fibers, increased cerebral blood flow, suppression of aberrant autoimmune responses, and stimulation of remyelination. We also discuss the observed failure of digestive function in MS and point out that pathological changes which parallel CNS findings have been found in the enteric nervous system (ENS) of patients with Parkinson's disease. Similar parallels might exist between the CNS and ENS in multiple sclerosis. (Altern Med Rev 2000;5(3):224-248.)

Introduction
A previous paper1 discussed preliminary results of usage of a transdermal histamine/caffeine preparation for ameliorating symptoms of multiple sclerosis (MS). Improvement was seen in 37 of 55 patients (67%) followed for at least six weeks. This work has continued, and at the time of writing 167 patients had been followed for at least six weeks, with 26 percent of patients experiencing significant improvement as defined previously,¹ 29 percent experiencing some improvement, and 45 percent seeing no benefit. Improvements at three months have, in most cases, continued at six months.

Areas of improvement have been observed in extremity strength, balance, bladder control, fatigue, heat tolerance, cognitive function, peripheral edema, and activities of daily living. Improvement is often seen within a few hours or days of starting therapy, and there have been minimal side-effects. This is in keeping with the findings of others who have administered similar amounts of subcutaneous histamine for such clinical problems as vertigo, headache,² and cancer.³

Five possible mechanisms of action of histamine on the symptoms and clinical manifestations of MS were introduced in Part One of this article.1 These include augmentation of subnormal cerebral tissue levels of histamine, improved electrical function of demyelinated fibers, increased cerebral blood flow, modulation of autoimmune responses, and stimulation of remyelination.

Although the respective bodies of literature on histamine and MS are vast, there are no recent studies exploring histamine's role in the treatment of MS, and only a few studies even tangentially examine the role of histamine in the pathophysiology of MS. A recent Medline search under the terms "histamine and multiple sclerosis" returned 16 citations, with only some of these papers relevant to the issues discussed here. Consequently, we emphasize that the ideas discussed here are mostly speculative and unsupported by direct experimentation. Should histamine therapy continue to show promise, we hope other researchers will use this paper as a starting point for testing these hypotheses.

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