Depression and Anxiety: Nutritional Considerations

Diet may influence mood in several ways. Certain amino acids and other nutrients act as cofactors in the production of neurotransmitters. Dietary carbohydrate and protein influence the rate at which neurotransmitter precursors enter the central nervous system from the blood. Caffeine and alcohol, of course, have pronounced nervous system effects. Weight loss in obese persons is associated with improvement in mood.⁹

Diabetes is associated with depression. Presumably, this is primarily because diabetes and its complications are likely contributors to depressive symptoms. However, poor metabolic control may exacerbate depression and diminish the response to antidepressants, and clinical studies have shown that, as metabolic control improves, so does depression.¹⁰ In addition, persons who are depressed are at increased risk for diabetes. A 2006 meta-analysis of 9 longitudinal studies found that individuals with major depressive disorder have a 37% increased risk of developing diabetes, compared to other persons.¹¹

The following nutrients are under investigation for their role in mood disorders:

Folate and Other B-Vitamins

Low blood concentrations of folate and vitamin B₁₂ correlate with depression in the general population.¹² The association between folate and depression may be mediated in part by elevated homocysteine levels, which are frequently found in depressed persons.^12,13 High plasma homocysteine has been associated with reduced levels of cerebrospinal fluid amine metabolites 5-hydroxyindole acetic acid (5-HIAA), homovanillic acid (HVA), and 3-methyl, 4-hydroxy phenylglycol.¹⁴

A common variant of the enzyme 5, 10-methylenetetrahydrofolate reductase (MTHFR) is significantly more common in individuals with elevated homocysteine or depression.¹⁵

Folic acid is important in the production of tetrahydrobiopterin (BH4), a co-factor in the conversion of phenylalanine to tyrosine and in the hydroxylation of tyrosine and tryptophan, rate-limiting steps in the synthesis of dopamine, norephinephrine, and serotonin. BH4 is also involved in regulating the presynaptic release of neurotransmitters from nerve terminals.¹⁴ Low blood-folate concentrations are associated with significantly greater risk for relapse in persons on antidepressant therapy,¹⁶ and folate status predicts response to antidepressant treatment in the elderly.¹⁷ Two clinical trials adding methyltetrahydrofolate (one at 500 µg/d; the other at 15 mg/d) to an antidepressant regimen further reduced depressive symptoms, as indicated by the Hamilton Depression Rating Scale.¹⁸

Observations that depression is associated with low levels of both vitamin B₁₂¹⁹ and pyridoxal phosphate²⁰ indicate that increasing dietary (and perhaps supplemental) intakes of these vitamins may be important in preventing or treating depression. Limited evidence suggests that geriatric patients with depression and cognitive dysfunction respond better to antidepressant medication when given supplemental vitamins B₁, B₂, and B₆, compared with antidepressant treatment alone.²¹

These observations may help explain why consuming a traditional Chinese diet, which is high in folate, with resulting high blood levels of this vitamin, is associated with lower rates of major depression.¹²

Omega-3 Fatty Acids

Depression is associated with lower levels of long-chain omega-3 fatty acids (ie, eicosapentanoic and docosahexanoic acids) in red blood cell membranes.²² Some, but not all, studies have found that in countries where intake of these fatty acids is higher, depression is less prevalent.²³ Among individuals in the Arctic, the abandonment of traditional diets high in omega-3 fatty acids has been associated with increasing rates of depression and anxiety,²⁴ although other biological and social factors may confound this interpretation.

Blood levels of polyunsaturated fatty acids predicted cerebrospinal fluid levels of both 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA).²⁵ Controlled clinical trials have found improvements in depression rating scales when fish oils were administered with standard antidepressants.^23,26,27 It is not known whether botanical sources of omega-3s, such as flax oil, have the same effect.

Botanical Treatments

St. John's Wort is effective in 50% to 70% of outpatients with mild depression.²⁸ However, minimal beneficial effects are found in larger studies in patients with major depression.²⁹ Passion flower (Passiflora incarnata), chamomile (Matricaria recutita), and lemon balm (Melissa officianalis) contain flavonoids that bind to benzodiazepine receptors, but only preliminary evidence supports their anxiolytic effects at this time.^6,28 Kava is an herbal treatment with evidence of a significant anxiolytic effect. However, it is no longer available, due to reports of liver failure in rare cases when high doses were taken.

The following treatments may be helpful, but require more study:

S-adenosylmethionine (SAMe)

Elevated concentrations of homocysteine often found in depressed persons may increase central nervous system (CNS) levels of S-adenosylhomocysteine, which has been shown to inhibit monoamine neurotransmitter metabolism. As the sole methyl donor in the CNS, SAMe is involved in the creation of monoamine neurotransmitters, membrane phospholipids, and proteins and nucleoproteins. Also, in limited trials SAMe has shown effects similar to those of medication in treating depression.³⁰ SAMe may have the advantages of a faster onset of action and fewer side effects, compared with selective serotonin reuptake inhibitors.³¹

Inositol

Inositol, a substance found in many foods (e.g., whole grain cereals, legumes) is a key intermediate of the phosphatidyl-inositol (PI) cycle, a second-messenger system used by several noradrenergic, serotonergic, and cholinergic receptors. Interest in inositol stems from the complaints of side effects caused by anxiolytic medications, leading patients to discontinue treatment and experience relapse.²⁸ Limited studies have suggested that at doses of 12-18 grams per day inositol reduces anxiety symptoms as effectively as selective serotonin reuptake inhibitors, with a low incidence of side effects.^32,33

Orders

See Basic Diet Orders chapter.

What to Tell the Family

Depression and anxiety are not simply volitional or temporary states of mind that can be easily changed. Depression in particular may arise from other diseases, and the presence of both disorders may indicate a need for more aggressive patient monitoring. Although they are medical disorders, depression and anxiety respond well in many cases to both medication and psychotherapy, and combining these treatments may be particularly effective. The role of folate and other nutrients is under investigation.