Adjusting both diet and nutrition may help some people with mental illnesses manage their symptoms and promote recovery. For example, research suggests that eliminating milk and wheat products can reduce the severity of symptoms for some people who have schizophrenia and some children with autism. Similarly, some holistic/natural physicians use herbal treatments, B-complex vitamins, riboflavin, magnesium and thiamine to treat anxiety, depression, drug-induced psychoses and memory loss. A number of herbs and dietary supplements have demonstrable effects on memory, mood, and insomnia⁴. There is a significant amount of evidence supporting the use of Gingko biloba and omega-3 fatty acids for dementia, as reviewed below. Many users of CAM may take a variety of herbal products⁵.

Ginkgo biloba leaf extract is among the most widely sold herbal dietary supplements in the United States. Its purported biological effects include scavenging free radicals, lowering oxidative stress, reducing neural damage, reducing platelet aggregation, and anti- inflammatory, anti-tumour and anti-ageing activities. Clinically, it has been prescribed to treat CNS disorders such as Alzheimer’s disease and cognitive deficits. It elicits allergy and changes in bleeding time. Its components, quercetin, kaempferol and rutin, have been shown to be genotoxic⁶ but the mutagenicity or carcinogenicity of Gingko biloba itself has not been reported. There are no standards or guidelines regulating the constituent components of Ginkgo biloba leaf extract, nor are exposure limits imposed. Safety evaluation of Ginkgo biloba leaf extract is being conducted by the US National Toxicology Program.

Ginkgo biloba has been widely used for many years by people with symptoms attributed to ‘cerebrovascular insufficiency,’ despite the lack of evidence of a causal role. Many placebo-controlled trials of Ginkgo biloba in patients with various types of dementia have yielded contradictory results. Of the studies that revealed any cognitive improvement, the effect was minor and did not last more than six months. Some studies reported haemorrhaging, indicating that it is necessary to use caution when prescribing Ginkgo biloba for cognitive deficits, especially in patients with increased risk of haemorrhage⁷. The recommended doses range widely, but in a trial of Alzheimer’s disease prevention, 120 mg of Gingko biloba twice a day was not effective in reducing the overall incidence rate of dementia or Alzheimer’s disease in elderly individuals with normal cognition or those with mild cognitive impairment⁸. Its short-term use is acceptable under some conditions, but the potential risk of bleeding must be seriously considered. Gingko biloba has been reported to reduce depression in dementia patients and counteract sexual side effects of antidepressants⁹.

The Use of Nutritional Supplements

In addition to herbal remedies, consumers use a variety of nutritional supplements (including vitamins, amino acids and fish oil) that may affect mood and functioning.

Elevated plasma homocysteine concentrations have been implicated with risk of cognitive impairment and dementia, but it is unclear whether low vitamin B12 or folate status is responsible for cognitive decline or can protect against it^10,11. Most studies reporting associations between cognitive function and homocysteine or B vitamins have used a cross-sectional or case-control design and have been unable to determine whether such associations are causal or merely a result of the disease. The homocysteine hypothesis of dementia has attracted considerable interest, as homocysteine can be easily lowered by folic acid and vitamin B12, raising the prospect that B-vitamin supplementation could lower the risk of dementia¹⁰. Incident dementia is more strongly associated with changes in folate, vitamin B12 and homocysteine, than with previous concentrations. These changes may be linked to other somatic manifestations of early dementia, such as weight loss¹². However, in a trial of high dose vitamin B in patients with Alzheimer’s disease, the supplement did not slow cognitive decline in individuals with mild to moderate Alzheimer’s disease¹³. Two other placebo-controlled trials of treatment with B12, folic acid and B6 showed no advantage of vitamins over placebo at reducing the severity of depressive symptoms or the incidence of clinically significant depression over a period of two years in older men¹⁴. Similarly, a recent Cochrane review found no evidence for short-term benefit from vitamin B6 in improving mood (depression, fatigue and tension symptoms) or cognitive functions. For the older people included in one of the two trials mentioned in the review, oral vitamin B6 supplements improved biochemical indices of vitamin B6 status, but potential effects on blood homocysteine levels were not assessed in either study. This review found evidence that there is scope for increasing some biochemical indices of vitamin B6 status among older people¹⁵. The limited available evidence suggests folate may have a potential role as a supplement to other treatments for depression. It is currently unclear if this is the case both for people with normal folate levels and for those with folate deficiency. More randomized controlled trials are needed to explore possible benefits from vitamin B6 supplementation for healthy older people and those with cognitive impairment or dementia.

Omega-3 Fatty Acids

Fish oil and omega-3 fatty acids are also commonly used supplements. Reductions in cardiovascular risk, depression and rheumatoid arthritis symptoms have been correlated with omega-3 fatty acid intake, and there is increased interest in the use of omega-3 fatty acid supplementation for other psychiatric illnesses and prevention of Alzheimer’s disease. Reported health benefits include improvements in cognition and mood in unipolar and bipolar mood disorders. Omega-3 fatty acids are found principally in fish and seafood although some can be derived from green vegetables. By contrast, omega-6 fatty acids are found in soft margarine, most vegetable oils and animal fat. Omega-6 is plentiful in most modern Western diets while omega-3 is often relatively lacking. A high dietary ratio of omega-6 to omega-3 has been linked to vulnerability to many physical and mental disorders¹. Most studies recommend omega-3 essential fatty acids with a ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) of 7:1. PUFA DHA 22:6(n – 3), a dietary essential, is important for maintaining normal nervous system function and cellular structure. A lack of DHA is associated with cognitive decline during ageing and neurodegenerative disease¹⁶. DHA-derived neuroprotectin D1 (NPD1) has recently been shown to provide homeostatic regulation of brain cell survival and repair involving neurotrophic, antiapoptotic and anti-inflammatory signalling¹⁶. Research suggests that growth factors and neurotrophins activate the synthesis of NPD1, which interacts with the molecular- genetic mechanisms affecting beta-amyloid precursor protein (betaAPP) and amyloid beta (Abeta) peptide neurobiology. Deficits in DHA or its peroxidation may play a role in inflammatory signalling, apoptosis and neuronal dysfunction in Alzheimer’s disease¹⁷‘¹⁸.

In a well-designed trial of the effect of EPA and DHA on mental well-being using a double-blind, placebo-controlled design in the general older population, the study failed to find drug-placebo difference in improving cognition or well-being¹⁸. In a meta-analysis, the authors concluded that available data are insufficient to draw strong conclusions about the effects of omega-3 fatty acids on cognitive function in normal ageing or on the incidence or treatment of dementia¹⁹. However, limited evidence suggests a possible association between omega-3 fatty acids and reduced risk of dementia.

In summary, omega-3 fatty acids may have a role in the treatment of late-life dementia, cognitive impairment and neuropsychiatric disorders. Future studies should clarify the function and the optimal dose of omega-3 fatty acids or EPA in the treatment of cognitive decline and address lingering questions regarding the purity of marketed supplements.

S-adenosyl-L-methionine (SAMe) is one of the CAM products that has been studied under rigorous controlled conditions. SAMe is a methyl donor involved in the synthesis of monoaminergic neurotransmitters derived from the amino acid L-methionine through the one-carbon cycle. SAMe has been investigated for its antide- pressant properties in both open¹ and randomized controlled²⁰ trials. SAMe dosages of 200-1600 mg/day (orally or parenterally) have been shown to be superior to placebo and as effective as tricyclic antidepressants in alleviating depression, although some individuals may require higher doses²⁰. At this time, the recommended doses range from SAMe 200 mg bid up to 800 mg bid. Oral dosages of SAMe up to 1600 mg/day appear to be significantly bioavailable and safe. SAMe has been associated with minor adverse effects, e.g. gastrointestinal symptoms and headaches¹, and an occasional induced mania²¹.

SAMe plays an essential role in maintaining neuronal health, and may prove to be an effective neuroprotective dietary supplement in Alzheimer’s disease. This disease is accompanied by reduced glutathione S-transferase (GST) activity, diminished SAMe, and increased S-adenosyl homocysteine (SAH), the downstream metabolic product resulting from SAMe-mediated transmethy- lation reactions. Panza et al. confirmed that SAMe can exert a direct effect on GST activity, thereby making SAMe an ideal neuroprotective candidate to slow the progression of Alzheimer’s disease²². It remains unclear if such supplements can reduce the risk for cognitive decline in very mild Alzheimer’s disease and mild cognitive impairment.