Essentials of Complementary and Alternative Medicine (June 1999)

Treatment Evaluation
There are three main outcome measures that are the focus of behavioral medicine practice and research: objective clinical outcomes, cost-effectiveness, and the 
subjective experience of the patient. First, objective clinical outcomes are necessary if behavioral medicine (or other complementary therapies) are to be considered 
viable alternatives or adjuncts to conventional medical care. Does this treatment reduce symptoms? Does this treatment improve the functional status of the patient's 
activities of daily living, ability to work, and so on? How does this treatment compare in effectiveness to other established treatments?
Although modifications of traditional double-blind, placebo-controlled studies may be necessary, behavioral medicine research is conducted using objective, reliable 
measures of clinical outcome, which are comparable to those measures used in studies of conventional therapies. However, because the scope of behavioral 
medicine extends beyond the basic organic pathology of disease, data about the patient's environment, thoughts and belief systems, associated physiological 
subsystems, and behavior, including relationships with others, are all elements of behavioral medicine outcome studies.
Second, the cost-effectiveness of behavioral medicine interventions is a critical variable in treatment evaluation. Research suggests that behavioral medicine 
treatments actually reduce overall medical costs, particularly with conditions such as chronic pain, asthma, and diabetes (
15
, 
64
, 
65
). There is an increasing 
awareness of both the high frequency of occurrence and increased cost and morbidity associated with untreated anxiety and depressive disorders that coexist with 
many chronic medical conditions (
13
, 
16
, 
19
, 
66
, 
67
 and 
68
). Again, research now supports the cost-effectiveness of programs designed to identify and treat patients 
who have such conditions (
69
, 
70
).
Third, behavioral medicine outcome research has focused on the subjective experience of illness and medical treatment. Hospital administrators and insurance 
carriers may refer to this dimension as customer satisfaction. From the patient's viewpoint, the important questions are, “Was I treated with dignity and respect?” and 
“Would I recommend this treatment to my friends or family?”
ORGANIZATION
In recent years, there has been a progressive re-integration of psychiatry (including behavioral medicine) and general medicine. Professional psychiatric 
organizations have joined with other medical specialty groups to lobby for legislation mandating parity for  cognitive services and mental health coverage for all 
patients. Departments of psychiatry within medical schools have refocused the curriculum for medical students and psychiatric residents to emphasize the 
developments in mind–body medicine. Psychiatric and behavioral medicine research has begun to establish both the clinical efficacy and cost-effectiveness of these 
approaches, and as a result there is an expanding presence of behavioral medicine services within general medical settings. However, despite these advancements, 
behavioral medicine services are still not covered by health insurance programs to the same extent as are more traditional medical treatments, such as surgery or the 
prescription of medication, even when benefits have been demonstrated.
PROSPECTS FOR THE FUTURE
Behavioral medicine is still significantly underused in the treatment of patients who have severe medical illness. However, because the origins of this treatment 
approach come from the practice of general psychiatry, the integration of behavioral medicine techniques into conventional medicine may be easier than that of 
alternative or complementary approaches, which have originated outside of standard medical practice. This is because conventional medical practitioners will 
probably offer less resistance to a treatment approach that is already perceived as part of the system. Further, the clinical effectiveness of behavioral medicine 
interventions, especially cognitive-behavioral therapies, in the treatment of patients with chronic medical illnesses should stimulate the growth of behavioral medicine 
programs. Health promotion and disease prevention is a natural area for expansion and integration of behavioral medicine programs within the general medical 
environment.
Behavioral medicine programs are useful adjuncts in the treatment of patients who have severe illnesses. Improved compliance with treatment, greater self-esteem, 
and better quality of life have all been demonstrated when behavioral medicine interventions are used in conjunction with standard medical treatment. Perhaps the 
greatest opportunity for the future, in light of these findings, is the integration of behavioral medicine techniques with standard medical practice to form a new 
alternative system of health care delivery (
71
).
Research attempting to elucidate the mechanisms of action of behavioral medicine interventions is in its infancy. Particularly exciting is the developing area of 
psychoneuroimmunologic research, which investigates the relationship between psychological status and immune functioning (
44
, 
45
). These and other areas of 
mind–body medicine offer promising new approaches to our understanding of human health and illness.

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CHAPTER 27. O
RTHOMOLECULAR
 M
EDICINE AND
 M
EGAVITAMIN
 T
HERAPY
Essentials of Complementary and Alternative Medicine
CHAPTER 27. O
RTHOMOLECULAR
 M
EDICINE AND
 M
EGAVITAMIN
 T
HERAPY
Alan R. Gaby
Background and Definition
 
Meganutrient Therapy: Theoretical Aspects
 
The Practice of Orthomolecular Medicine
Provider-Patient Interaction
Orthomolecular Therapy and Outcomes
Use of the System for Treatment
 
Congestive Heart Failure
 
Osteoarthritis
 
Gingivitis
 
Fatigue
 
Kidney Stones
 
Osteoporosis
 
Orthomolecular Psychiatry
 
Intravenous Nutrient Therapy
 
EDTA
 
Other Uses of Orthomolecular Medicine
 
Toxicity
Organization
 
Training
 
Reimbursement Status
 
Relations with Conventional Medicine
Prospects for the Future
Chapter References
BACKGROUND AND DEFINITION
Orthomolecular medicine is the use of molecules normally present in the body for the prevention and treatment of disease. In 1968, Linus Pauling, PhD, introduced 
the concept of orthomolecular medicine (
1
), a term he invented to denote “the right molecules.” It was Pauling's contention that adjusting the concentrations of 
molecules (e.g., vitamins, minerals, amino acids, hormones, and metabolic intermediates) that are normally present in the body is one effective approach to the 
prevention and treatment of disease. Orthomolecular medicine is both a concept and a treatment modality. Practitioners who use orthomolecular medicine believe that 
increasing or decreasing the concentration of certain naturally occurring molecules can have a beneficial effect on various disease processes.
Some treatments that are considered orthomolecular are also well accepted in the practice of medicine. For example, the management of phenylketonuria includes 
dietary changes designed to reduce the concentration of phenylalanine; vitamin B
6
–dependent seizures are controlled by large-dose supplementation of vitamin B
6
; 
and insulin injections are given to diabetics who have a deficiency of (or resistance to) insulin. More recently, there has been growing acceptance of the idea that 
administering folic acid and vitamin B
6
 may reduce the risk of cardiovascular disease by lowering homocysteine concentrations (
2
). Other orthomolecular treatments 
are more controversial, such as the use of large doses of niacinamide to treat schizophrenia or the use of vitamin C to treat the common cold and other viral illnesses 
(
3
).
The rationale for using orthomolecular therapies may differ from one treatment to another, and some of the theoretical reasons for using meganutrient therapy are 
covered in this chapter. However, not all orthomolecular treatments have a clear rationale; some have been developed primarily through empirical observation. In 
many cases, nutrient doses have also been derived empirically, and the optimal doses may still be unknown.
In some cases, an orthomolecular treatment is nothing more than replacement therapy, as with the use of vitamin C to treat scurvy. In other cases, natural substances 
are used in doses beyond those normally required to correct a deficiency. However, it is sometimes difficult to distinguish between replacement therapy and 
“purposeful loading.” For example, supraphysiological doses of insulin may be needed not only to correct insulin deficiency, but also to overcome insulin resistance. 
And, although elevated serum concentrations of homocysteine can result from deficiencies of vitamin B
6
 or folic acid, some patients need higher-than-normal amounts 
of these vitamins to compensate for genetic defects in homocysteine metabolism.
Although all physicians practice orthomolecular medicine to some extent, only a small minority of them consider it their primary treatment modality. However, interest 
in this approach has been increasing because of the growing body of scientific literature documenting the effectiveness of various natural substances. In addition, 
these substances may often be safer and less expensive than conventional drugs and surgery.
Meganutrient Therapy: Theoretical Aspects
Orthomolecular medicine frequently involves the use of vitamins, minerals, amino acids, and other substances in amounts greater than the Recommended Dietary 
Allowance (RDA). It is important to recognize that the RDAs were designed to prevent nutritional deficiency diseases in the majority of the healthy human population. 
In formulating the RDA, the Committee on Dietary Allowances did not address the issue that larger doses of nutrients might produce benefits that extend beyond 
merely preventing deficiency.
The RDA by definition applies only to healthy individuals, not to those with physical or mental illness (
4
). Some individuals may become ill simply because they have 
higher-than-normal nutritional requirements that are not met by their diet. Extreme examples of this can be seen in the various inborn errors of metabolism that result 
in nutrient-dependency syndromes. For example, individuals with primary hyperoxaluria develop multiple calcium oxalate renal stones (which can progress to renal 
failure) unless they receive massive doses of pyridoxine (vitamin B
6
). Although most of the well-characterized nutrient-dependency syndromes are rare, it is likely that 
milder versions of these or similar conditions are prevalent in a larger proportion of the population.
In addition to correcting nutritional deficiencies and dependencies, nutrients exert pharmacological effects that may be clinically useful. For example, ascorbic acid at 
high concentrations in vitro is both virucidal (
5
) and antibacterial (against  Mycobacterium tuberculosis, Escherichia coli, and Pseudomonas aeruginosa) (
6
, 
7
). The 
concentrations of ascorbic acid that produce these antimicrobial effects are obtainable in vivo by intravenous administration of vitamin C. Vitamin B
6
 (in lozenge form) 
can prevent dental caries by shifting the balance of oral flora (
8
).
Pharmacological doses of nutrients also have the capacity to alter human biochemistry by activating or inducing the synthesis of enzymes, by inhibiting enzyme 
breakdown, or by other mechanisms. For example, vitamin B
6
 can inhibit the endogenous synthesis of oxalate, thereby reducing the risk of calcium oxalate urolithiasis 
(
9
). Large doses of vitamin E inhibit platelet aggregation, which may be valuable in the prevention of cardiovascular disease (
10
). Magnesium has been shown to 
exert a bronchodilating effect in asthmatics (
11
). Some nutrients serve as precursors for neurotransmitters, prostaglandins, and other biologically active compounds. 
Thus, administration of tryptophan and choline have been shown to increase the concentrations of serotonin and acetylcholine, respectively (
12
). Supplementation 
with specific essential fatty acids has produced anti-inflammatory effects, probably by altering the ratio of certain prostaglandins (
13
).
Other biochemical or physiological abnormalities that may be indications for nutrient supplementation include malabsorption, defective transport of nutrients into cells 
or across the blood-brain barrier, or a genetically abnormal enzyme that has a reduced affinity for its cofactor (usually a vitamin or mineral) (
14
). Disease processes 
(or the drugs used to treat them) may also increase nutritional requirements.

Thus, high-dose nutrient therapy can exert a wide range of physiological and pharmacological effects. These diverse actions have been listed to help create a 
conceptual framework that can be used to explain the observed benefits of orthomolecular treatments. It should be noted, however, that orthomolecular medicine is 
still in its infancy, and there are still many unknowns concerning mechanisms of action, choice of appropriate patients for treatment, and optimal nutrient doses.