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What’s the Point of
Nutrition and Mental Health?

Professor Ben Green, University of Chester and Cheadle Royal Hospital
A review paper based on presentation at Mental Health and Nutrition Conference, Cheadle Royal Hospital, Manchester, February 25th 2009

Introduction

There is a vast overlap between nutrition and mental health that is not reflected sufficiently in current research or practice. Partially this may be because of some perception that the area is somewhat faddy and partially this may be because there is no practical way to produce 'magic bullet' foods that are patentable in quite the same way as pharmaceuticals. Pharmaceutical companies are unlikely to sponsor research which drives a nutritional treatment approach. Responsibility for commissioning reasonable and thorough research would therefore rest quite squarely with Government agencies and national health providers. There are nutritional research programs, but mental health is not featured fairly in proportion to the other aspects of medicine. This must change.

In making a case for the consideration ofnutrition in mental health being a fundamentaly important area I would like to review what we already know about various key areas and their imapct on mental health.

I will therefore cover in this paper:

deficiencies,
toxicities,
drugs and alcohol
eating disorders
lipids, diabetes mellitus, metabolic syndrome and schizophrenia
abnormal food choices, contaminated food supplies and prion diseases

Deficiencies

The developed world provides arelatively food-rich environment, at least in terms of calories. Ignorance of nutriotional requirements or bad or idiosyncratic dietary habits may however lead to deficient diets. In world areas where poverty or economic depression blights existence human diets may be deficient both in terms of calories and specific nutrients.

A prime example of a deficiency with mental health relevenace is scurvy. Scurvy has long been recognised as a problem associated with deficient diet, but only in the alst few hundred years ahs the specific lack of vitamin C as a cause of scurvy been identified. Vitamin C (or ascorbic acid) is found in fresh vegatbles and fruit.

Vitamin C deficiency has been associated with sudden-onset, profound suicidal depression, and was described in in 18th century sailors on long voyages with deficient diets of ship’s biscuit, grog and salt pork and due to long periods out at sea - a lack of fresh food

The first use of fruit as anti-scurvy agent was reportedly in 1601 by James Lancaster, but it was many, many decades later before the Royal Navy used anti-scurvy foods as per any coherent medical policy.

Vitamin C deficiency is associated with:

•Problems with protein production and tissue repair
•Weakness, lethargy and depression
•Anaemia
•Breakdown of old scars
•Bleeding gums
•Loss of teeth
•Splinter haemorrhages

Depression may be early sign of vitamin C deficiency, that occurs as a haerald symptom, ie before other physical manifestations. For instance, the Minnesota Multiphasic Personality Inventory (MMPI) changes begin at 1.21-1.17 mg/100 ml for blood vitamin C, whereas physical changes start later at 0.67-0.14 mg/100 ml (Kinsman & Hood).
The associated affective symptoms do not resolve until body pool of vitamin C is replenished

Thiamine deficiency results in one of the key mental health problems seen in alcohol dependence manifesting in memory problems due to micro-organic haemorrhages and brain pathology as per the Wernicke-Korsakoff syndrome.

The Wernicke portion of the syndrome, (the encephalopathy) is the acute phase of the disorder with symptoms and signs including:

•Glove and stocking neuropathy
•Disorientation and confabulation
•Memory disturbance
•Ataxia (staggering)
•Lateral nystagmus

The Korsakoff portion is a more chronic entity characteristically associated with short term memory disturbance.


Carl Wernicke	Sergei Korsakoff

Thiamine deficiency has other links to psychiatry – for instance in association with a high carbohydrate diet in affluent society, there have been reports of thiamine deficiency producing irritability/hyperactivity in children (Lonsdale, 2006). [This compares to original condition beri-beri in diets of polished rice - in Japan]. Marginal thiamine deficiencies may be also be reportedly mistaken for ‘functional’ illness e.g. aggression, sleep apnoea.

There has been some work associating agoraphobia – with abnormal thiamine, niacin and pyridoxine tests, (Abbey, 1980). [ The proposed mechanism linking deficiency to symptomatic involves raised lactic acid levels, and under production of GABA]

In addition iron deficiency has been traditionally linked to tiredness, reduced psychomotor scores and depression (also some studies link low zinc to treatment resistant depression).

Folate deficiency has been linked to depression - Herbert's 1962 work found depression occurring after a 4/12 self-induced folate deficient diet – he noted his own symptoms of insomnia, irritability, fatigue and forgetfulness. Any measurable anaemia post-dated this (18/52) so again mental symptoms of deficiencies may pre-date biological screening abnormalities.

A recent Cochrane review quoted 2 studies which found addition of folate may improve Hamilton scores of depressed patients 2-3 points beyond antidepressants alone.

There is similar evidence linking B12 deficiency to abnormal low mood as also for iodine and selenium deficiencies.

Dietary Contaminants

•Heavy metals- lead, mercury (e.g. fish, medicines) - can lead to potential neurotoxic effects including sleep disturbance, cognitive impairment, aggression, emotional lability
•Thallium – psychosis, convulsions, memory loss
•Depending upon how stringently you construe them, drugs and alcohol could be termed contaminants of a natural diet! Drugs including alcohol may have severe and longstanding effects on mental health that are far too numerous to detail in this short paper. Caffeine obviously affects sleep, alertness, and increases respiratory rate, and may provoke anxiety. Caffeine is also associated withdrawal syndrome– e.g. headache and reduced cognitive performance.

Errors of Metabolism

Such errors may convert a normal diet into one which is associated with internal excesses or deficiencies that may affect brain function. Such an example may include Phenylketonuria (discovered by Dr Foling in 1934). Phenylketonuria is an inherited condition involving an autosomal recessive inheritance and chromosome 12. In this error of metabolism there is a lack of the enzyme phenylalanine hydroxylase leading to raised levels of the amino acid phenylalanine in the months after birth and consequent brain damage producing learning disability and seizures.

Phenylketonuria is one of the few genetic diseases that can be prevented by diet alone, (if detected at birth by HPLC or Guthrie tests) and affects about 1 in 15,000 live births.

Other internal metabolic conditions leading to brain damage may involve copper deposition (Wilson's disease) and dementia.

Nutritional problems: anorexia nervosa and other eating disorders

•Starvation and deficiencies (may be idiosyncratic depending on individual dietary restrictions)
•38% severe anorexia patients are thiamine deficient (cognitive effects, cardiac failure)
•Re-feeding syndrome (Solomon & Kirby, 1990)– delayed gut motility/constipation/impaction – judicious calorie increases
•Re-feeding electrolyte disturbances- hypokalaemia, hypocalceamia, hypomagnesaemia (60%), hypophosphataemia)
•Refeeding oedema/cardiac failure
•Others: Carotenaemia

Dementia and nutrition

•Deficiencies of B12/folate usually screened for in dementia clinics – reversible causes of cognitive impairment in elderly
•Bad food choices may also be important e.g. human brain tissue in cannibalistic practices where relatives consume the life force of the deceased > prion disease> kuru in Papua New Guinea - (Characterised by tremor, truncal ataxia, dementia, emotional incontinence) Incubation period of 14 - 40 years approx, with early susceptibility being genetically determined.
•New Variant Creutzfeldt-Jakob Disease also associated with prions – 1997 finding of vCJD in Kentuckians who ate squirrel brains.
•'We must not forget that almost every person in the UK was exposed to the agent that causes variant CJD. It went through the entire food chain, not just in burgers but in cakes containing gelatins made from meat products. Even cosmetics contained beef-derived chemicals then.’ Professor John Collinge, head of the MRC's prion unit in London, 2008. It may be that the first wave of cases were in genetically highly susceptible individuals – with so called ‘double m’ genes- and that and larger second wave (amongst those with double v genes) is due in the next few decades.

Diabetes and Schizophrenia

•Predicted 72% increase in overall prevalence of diabetes mellitus by 2025
•1897- Henry Maudsley (of Maudsley Hospital and Cheadle Royal) notes ‘diabetes is a disease which often shows itself in families where insanity prevails’
•1919 Kooy notes increased blood sugar in 10 people with schizophrenia against control group of 20
•Some studies (Ryan 2003, Takore et al, 2002) note association between schizophrenia and diabetes independent of antipsychotics
•Antipsychotics promote weight gain and increase risk of precipitating diabetes (highest risk olanzapine and clozapine)

•Theories behind association: dysregulation of hypothalamic-pituitary-adrenal axis due to stress, raised cortisone, then diabetes ; self neglect, smoking, lack of exercise, poor diet; weight gain induction by antipsychotic drugs.
•Pre-antipsychotic drugs (introduced from 1953 onwards) insulin therapy was used. In 1940s Sargent wrote: “In a series of over 400 patients treated in Swiss hospitals before 1937, when the technique was still new, 59 per cent. of persons treated within the first six months after onset reached either a complete or social remission”

Lipids and schizophrenia

•Paton et al (2004) found dyslipidaemia in 68% of UK patients on antipsychotics
•Saari et al (2004) in Finland found significantly increased cholesterol and triglycerides in patients on antipsychotics- also in 2005 found 3.7 x risk of metabolic syndrome in schizophrenia
•(Metabolic syndrome incorporates hyperglycaemia, obesity, high blood pressure, deranged lipids)

Omega-3 and schizophrenia

•Omega 3 touted to be effective in depression, bipolar disorder and schizophrenic negative symptoms in 1990s
•Possible role in reducing irritability in bipolar patients in open label study (Sagdayu, 2005)
•Cochrane reviews (2006) found no clearly significant effects in schizophrenia
•Adverse effect of diarrhoea noted by Cochrane with omega-3 – 40 week study also noted weight gain and increased bleeding time (Emsley et al, 2008)
•Cochrane advised larger, well-designed studies
•Omega-3 may be useful in ameliorating triglyceride levels in patients who must take clozapine (Caniato et al, 2006) - 22% reduction in serum triglyceride levels in patients taking 10g of fish oil
•Omega 3 touted to be effective in depression, bipolar disorder and schizophrenic negative symptoms in 1990s
•Possible role in reducing irritability in bipolar patients in open label study (Sagdayu, 2005)
•Cochrane reviews (2006) found no clearly significant effects in schizophrenia
•Adverse effect of diarrhoea noted by Cochrane with omega-3 – 40 week study also noted weight gain and increased bleeding time (Emsley et al, 2008)
•Cochrane advised larger, well-designed studies
•Omega-3 may be useful in ameliorating triglyceride levels in patients who must take clozapine (Caniato et al, 2006) - 22% reduction in serum triglyceride levels in patients taking 10g of fish oil

Epilogue

•Significant overlap between nutrition and mental health
•You can’t patent food like drugs and pharma monies not available for research
•Area therefore probably under-researched compared to potential impact
•Warrants increase in Government / MRC sponsored research - dedicated programme for nutrition and mental health

References

•Abbey, LC (1980) Agoraphobia
•Caniato, RN, Alvarenga ME, Garcia-Alcaraz MA (2006) Effect of omega-3 fatty acids on the lipid profile of patients taking clozapine. Aus & NZ J of Psychiatry. 40(8):691-7.
•Emsley R et al. (2008) Safety of the omega-3 fatty acid, eicosapentaenoic acid (EPA) in psychiatric patients: results from a randomised, placebo-controlled trial.Psychiatry research. 161 (3) 284-291.
•Joy, CB, Mumby-Croft R, Joy LA. Polyunsaturated fatty acid supplementation for schizophrenia. Cochrane database. Updated 2006
•Kinsman R A & Hood J. Some behavioral effects of ascorbic acid deficiency, 455-464.
•Kooy, F H. (1919)Hyperglycaemia in mental disorders. Brain, 42, 214-288.
•Lonsdale, D. (2006) Review of the biochemistry, metabolism and clinical benefits of thiamine and its derivatives. Evidence based complementary and alternative medicine.
•McNamara et al (2007) Abnormalites in the fatty acid composition of the PM oribitofrontal cortex of schizophrenic patients: gender differences and partial normalization with antipsychotic medications. Schizophrenia Research.
•MRC- Human Nutrition Research http://www.mrc-hnr.cam.ac.uk/
•Paton C et al (2004) Obesity, dyslipidaemia and smoking in an inpatient population treated with antipsychotic drugs. Acta Psychiatr. Scand, 110, 299-305.
•Reddy, RD, Keshavan, MS, Yao, JK. (2004) reduced red blood cell membrane essential polyunstaurated fatty acids in first episode schizophrenia at neuroleptic-naïve baseline. Schizophrenia Bulletin, 30(4): 901-11.
•Ryan MC et al (2003) Impaired fasting glucose tolerance in first episode, drug naive patients with schizophrenia. Am J. Psychiatry, 160, 284-289.
•Saari et al (2004) Serum lipid in schizophrenia and other functional psychoses: a general population norhern Finland 1966 birth cohort survey. Acta Psychiatr Scand, 110, 279 – 285.
•Sagdayu K et al. (2005) Omega-3 fatty acids decreased irritability of patients with bipolar disorder I and add-on, open label study. Nutrition Journal.
•Sargent, W. (1944) Insulin Treatment of Schizophrenia.http://priory.com/homol/insulin.htm
•Thakore J H et al (2002) Increased visceral fat distribution in drug-naïve and drug-free patients with schizophrenia. Int. J. Obes. Relat. Metab. Disord, 26, 137-141.