Deficiencies of members of the vitamin B complex appear to be common in patients with agoraphobia (fear of open spaces).¹ The same is likely to be true for other anxiety-related conditions. We will review the evidence suggesting that individual members of this family may affect the experience of anxiety.

Inositol Supplementation
Inositol is a key intermediate of the phosphatidyl-inositol cycle, a second-messenger system used by several noradrenergic, serotonergic and cholinergic receptors.² Since ingestion has been shown to raise inositol levels in the cerebrospinal fluid,³ this nutrient could potentially serve as an anti-anxiety agent.

Indeed, when a group of 21 patients with panic disorder either with or without agoraphobia received 12 grams daily of inositol or placebo in random order for 4 weeks each, the inositol supplement was associated with a significantly greater reduction in the frequency and severity of panic attacks and of agoraphobia than the placebo. Moreover, while the efficacy of the nutrient was judged to be comparable to that of imipramine, its side effects were minimal.⁴

Niacinamide Supplementation
Niacinamide has been shown in an animal study to have benzodiazepine-like actions including anti-conflict, anti-aggressive, muscle relaxant and hypnotic effects.⁵ In contrast to niacin, it passes readily from the plasma to the cerebrospinal fluid where it is taken up into brain cells by a high-affinity accumulation system,⁶ suggesting it is the preferred form of vitamin B3 for the treatment of anxiety.

Lactate (which is associated with anxiety) reacts with niacinamide-adenine dinucleotide [NAD+] to form pyruvic acid and reduced NAD (NADH + H+). The equilibrium of this reaction favors lactate and NAD+, but it can be driven by adding excess NAD+. It may be that supplementation with niacinamide helps to drive the reaction, thus reducing lactate concentrations.⁷

Anecdotal reports suggest that niacinamide has anxiolytic effects comparable to the benzodiazepines,⁸ and it may be particularly effective for patients whose anxiety is secondary to reactive hypoglycemia.⁹ Typical dosages are between 500 mg twice daily and 1,000 mg 3 times daily.9 Hoffer believes that the optimal daily dosage is just below the amount that produces nausea.¹⁰

Thiamine Deficiency
Elevated lactate may also be caused by inadequate pyruvate dehydrogenase activity resulting from a thiamine deficiency or dependency. In that case, the conversion of pyruvate to acetyl CoA is inhibited, fostering its conversion to lactic acid.¹¹ Symptoms of a prolonged moderate thiamine deficiency may include fearfulness progressing to agitation as well as emotional instability and psychosomatic complaints.¹²

When more than 1,000 healthy young men were studied, those who were chronically borderline thiamine-deficient were currently feeling significantly more anxiety—although they were not customarily nervous individuals.¹³ There are no published studies on the repletion of a borderline thiamine deficiency to treat anxiety.

Vitamin B6 Deficiency
Gamma aminobutyric acid (GABA), an inhibitory neurotransmitter which is involved in the regulation of anxiety, requires vitamin B6 for its synthesis; thus a deficiency of this vitamin may theoretically result in heightened anxiety. Vitamin B6 is also required for the conversion of tryptophan to serotonin, a neurotransmitter suspected of being involved in anxiety.¹⁴

When over 1,000 healthy young men were studied, those found to be chronically deficient in vitamin B6 had a significantly greater tendency to become anxious, although they were not significantly more anxious at the time of the study.¹³ Also, in an open trial, patients with hyperventilation syndrome who also had abnormal xanthurenic acid excretion (an indicator of vitamin B6 deficiency) improved following the administration of pyridoxine and tryptophan, suggesting that a marginal B6 deficiency, by causing serotonin depletion, may have produced the syndrome.¹⁵

Vitamin B12 Deficiency
Anxiety may be part of the neuropsychiatric syndrome seen in advanced cases of pernicious anemia which is well-known to be caused by B12 deficiency.¹⁶ When cobalamin levels of more than 1,000 healthy young men were studied, those who were chronically borderline vitamin B12-deficient were significantly more anxious at the time of the study—although they were not customarily nervous individuals.¹³ Whether B12 supplementation reduces anxiety when the vitamin is borderline deficient remains to be investigated.

Doctor Werbach cautions that the nutritional treatment of illness should be supervised by physicians or practitioners whose training prepares them to recognize serious illness and to integrate nutritional interventions safely into the treatment plan.

References
1. Abbey LC. Agoraphobia. J Orthomol Psychiatry 11:243–59, 1982
2. Benjamin J et al. Inositol treatment in psychiatry. Psychopharmacol Bull 31(1):167–75, 1995a
3. Levine J et al. Inositol treatment raises CSF inositol levels. Brain Res 627(1):168–70, 1993
4. Benjamin J et al. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. Am J Psychiatry 15(7):1084–6, 1995b
5. Möhler H et al. Nicotinamide is a brain constituent with benzodiazepine-like actions. Nature 278:563–5, 1979
6. Hankes LV. Nicotinic acid and nicotinamide, in LJ Machlin, Ed. Handbook of Vitamins. New York, Marcel Dekker, 1984:329–77
7. Wendel OW, Beebe WE. Glycolytic activity in schizophrenia, in D Hawkins & L Pauling, Eds. Orthomolecular Psychiatry: Treatment of Schizophrenia. San Francisco, W. H. Freeman, 1973
8. Prousky JE. Niacinamide’s potential role in alleviating anxiety with its benzodiazepine-like properties: a case report. J Orthomol Med 19(2):104–110, 2004
9. Gaby AR. Vitamin B3 (Part 2): Powerful tool in nutritional medicine. Nutrition & Healing December, 1995
10. Hoffer A. Vitamin B-3: niacin and its amide. Townsend Letter for Doctors and Patients 147:30–39, 1995
11. Wick H et al. Thiamine dependency in a patient with congenital lactiacidaemia. Agents Actions 7(3):405–10, 1977
12. Williams RD et al. Induced thiamine (Vitamin B1) deficiency in man; relation of depletion of thiamine to development of biochemical defect and of polyneuropathy. Arch Intern Med 71:38–53, 1943
13. Heseker H et al. Psychological disorders as early symptoms of mild-moderate vitamin deficiency. Ann NY Acad Sci 669:352–7, 1992
14. Johnston AL, File SE. 5-HT and anxiety: promises and pitfalls. Pharmacol Biochem Behav 24(5):1467–70, 1986
15. Hoes M et al. Hyperventilation syndrome, treatment with L-tryptophan and pyridoxine; predictive values of xanthurenic acid excretion. J Orthomol Psychiatry 10(1):7–15, 1981
16. Ambrosino SV. Neuropsychiatric aspects of pernicious anemia: report of a case. Psychosomatics 7(1):24–8, 1966

Updated from Werbach MR with Moss J. Textbook of Nutritional Medicine. Tarzana, California, Third Line Press, Inc., 1999.

In Foundations of Nutritional Medicine, one of Dr. Werbach’s internationally acclaimed Sourcebooks of Clinical Research, health practitioners concerned with nutritional influences on illness will find valuable information which will improve the quality of their practices. A free brochure describing all of his books is available from Third Line Press, 4751 Viviana Drive, Tarzana, California 91356. (800–916–0076; 818–996–0076; FAX: 818–774–1575; E-mail: tlp@third-line.com; Internet: http://www.third-line.com)