ADHD, Ritalin & What Doctors don't tell you
"Considerable evidence is accumulating that deficiencies in the body's reserve or production of fatty acids is a major contributory factor in a range of interrelated childhood disorders, including ADHD, dyslexia, asthma, allergies and even autism, and that fatty acid supplementation is valuable in a significant number of cases."
This specialist magazine gives a comprehensive viewing of the various issues surrounding the various nutritional links being investigated in relation to ADHD and other learning conditions.
The author, Simon Best, can be found on:
ATTENTION DEFICIT DISORDER
Inventing the syndrome to sell the solution?
One in seven children in the US and a rapidly growing number in the UK are being given stimulants with a long list of side effects to treat a condition that may be due to a simple deficiency of certain vital nutrients, as Simon Best reports.
Attention Deficit/Hyperactivity Disorder (ADHD) in children is fast becoming one of the most over-diagnosed and -- many would argue -- over-prescribed pediatric disorders both in the US and now in Great Britain. It is certainly one of the most fiercely debated.
In the US, its incidence is estimated at 3-5 percent and up to 10 percent if less stringent criteria are used. In the UK, 2 percent of children aged 6-16 are diagnosed hyperactive, with 69,000 considered to be suffering from 'severe ADHD' (Baldwin S. Crit Pub Health 2000;10(4):453-62).
While many argue over what constitutes ADHD, the medical profession -- especially in the US -- tends to speak with one voice as to the solution. Since the 1960s, the psychostimulant Ritalin, generically known as methylphenidate hydrochloride (MPH), an amphetamine-like addictive drug that mimics the biochemical properties of cocaine -- has been administered to thousands of children. It is now estimated that up to one in seven American children is being given the substance daily.
A similar staggering increase in use has been recorded in the UK, where MPH is designated a class B controlled drug (class A if it were in solution).
Professor Steve Baldwin of the University of Teeside states that the rate has increased 15-fold, from 6,000 prescriptions a year here in 1994 to 92,000 in 1997 (Crit Pub Health, ibid). By 1999, this had reached 131,000 (covering some 21,000 children), but this is likely to be a gross underestimation because official statistics (based on pharmacy returns) do not include prescriptions given out in private practices, young offender centres or residential homes.
In France, MPH use is rare, and in the rest of Europe its prescription for minors is either uncommon or unheard of. However, Baldwin and colleague Rebecca Anderson estimate that if MPH prescriptions were allowed to double year by year, by 2007, the UK would match the US in having one in seven schoolchildren taking the drug daily (Crit Pub Health 2000;10(1):81-6).
All the indications suggest that drug companies have just this kind of scenario in mind. Since the end of 1999, the leading manufacturer of MPH -- Novartis (formally Ciba Geigy and Sandoz) -- has lost its sole product license for the compound (as Ritalin), allowing other companies to launch their own brands (such as Equasym by Medeva), while three others -- Mallinckrodt Inc, Schein Pharmaceuticals and MD Pharma -- are in the process of preparing products (Crit Pub Health, ibid).
The Selling of Ritalin
In the US, where Ritalin was first used in 1955, Novartis and other drug companies producing similar drugs used on children, such as dextroamphetamine and metamphetamine, have been very successful in persuading psychiatrists and health authorities of the alleged benefits of these drugs despite their potential risks and contraindications.
MPH is not licensed for children under the age of six (although, in practice, it is given to those as young as three) nor is it for those who suffer marked anxiety, agitation or tension; or those who have symptoms or a family history of tics or tourette's syndrome; hyperthyroidism; severe angina or cardiac arrhythmia; glaucoma; or thyrotoxicosis (an excess of thyroid hormones). Caution is required in the prescribing of MPH for children and young people with epilepsy or psychotic disorders, or a history of drug or alcohol dependence.
Proponents assert that MPH works by correcting a 'brain disorder', 'biochemical imbalance' or 'biological dysfunction' but no scientific rationale for MPH prescription has ever been made explicit by its adherents (Jensen PS et al. unpublished paper, Walter Reed Army Inst. Washington, 1989; Barkley RA et al. Pediatrics 1989;86:184-92; Kewley G. BMJ 1998;314:1594-5).
In November 1998 the US National Institute of Health held a consensus development conference on the diagnosis and treatment of ADHD. The 31 expert panel members (including psychiatrist Dr Peter Breggin, one of America's fiercist critics of MPH), noted that there were 'no data to indicate that ADHD is due to a brain malfunction.' or that it might be a disease state or brain pathology.' (NIH, Rockville, 1998;)
Despite this, the pro-Ritalin lobby cites a large-scale multiple treatment study of ADHD -- the MTA Study -- sponsored by the National Institute of Mental Health and carried out at six separate sites (MTA Cooperative Group, Arch Gen Psychiat 1999;56:1073-86). The Ritalin lobby claims that the results showed the superiority of stimulant treatment over behavioural and other treatments (although no nutritional alternative was tested in the trial).
However, Dr Breggin, at John Hopkins University's Education Faculty and author of Talking Back to Ritalin (Maine: Common Courage Press, 1998 - see www.breggin.com) has written a 16-point rebuttal of the MTA Study that severely undermines its credibility and findings. Chief among his criticisms is that it was not a placebo-controlled, double-blind trial.
Furthermore, the blind classroom raters found no difference between any of the treatment groups, there was no control group of untreated children, the children themselves did not rate themselves as improved, and out of 4,541 children originally screened, only 2.7% (123 children) completed the medication management trial.
This demolishing of the MTA Study is particularly important because in the UK the National Institute for Clinical Excellence issued its guidance on the use of MPH last October (NICE, 2000, Technology Guidance No 13; see: www.nice.org.uk). It accepts the official MTA results with little critical analysis, even referring to it as 'well conducted'. The NICE report basically endorses the use of MPH, although it does acknowledge that 'if improvement of symptoms is not observed ... over one month, the drug should be discontinued.'
However, it does not mention that about 30 percent of children show no response, or that up to 50% show side-effects. Professor Baldwin states:
'Adverse drug reactions and side-effects (more accurately described as 'main effects') from MPH include: CNS sequelae, gastro-intestinal effects, cardiovascular effects, liver abnormalities, convulsions (including grand mal), drug dependency and addiction, drug withdrawal reaction, hair loss, low white blood cell count, agitation, hostility, depression, psychotic depression, abnormal thinking, hallucinations, psychoses, emotional lability, overdose and suicide (Ethical Hum Sci Services 1999;1(1):13-33).
'Paradoxically, the supposed desirable bahavioural effects (including passivity, attention, reduced spontaneity) are the primary toxic effects of psychostimulants.' [Baldwin's italics]. In effect, the 'efficacy' of MPH involves serious adverse effects.
The NICE Report only mentions nervousness and sleeplessness as common MPH side-effects, and claims that the other effects reported were 'relatively minor'.
Despite the general acceptance by the US and UK psychiatric community to medicate this highly controversial disorder, there are now signs that the debate has reached a turning point. Recently, various legal actions have been launched in the US against not only Novartis, but also the American Psychiatric Association for alleged fraud and corruption, with similar actions pending in the UK.
As the problems with MPH have surfaced, so have promising non-drug treatments, specifically growing evidence for nutritional and heavy metal detoxification treatments.
Nutritional Approaches
Twenty years ago, Sally Bunday and her mother, the late Irene Colquhoun, founders of the Hyperactive Children's Support Group in the UK, were the first to propose that essential fatty acid (EFA) deficiency might be a factor in ADHD (Colquhoun I, Bunday S. Med Hypotheses 1981;7:673-9).
Surveying a group of hyperactive children they found an excess of males, a link with asthma, eczema and other allergic conditions, and evidence from hair analysis of zinc deficiency. Clinical signs, such as excessive thirst, frequent urination, dry skin and dry hair, were observed that are consistent with EFA deficiency.
In the US, a diet developed by the late paediatrician Dr Benjamin Feingold (Am J Nursing 1975;75:797-803; Why your Child is Hyperactive, Random, NY, 1975) was designed to eliminate certain synthetic additives and particular foods, especially fruits, containing natural salicylates, which inhibit the conversion of long-chain polyunsaturated fatty acids to prostaglandins (see below).
The diet was successful in reducing symptoms and groups sprung up all across the US and remain active in promoting and researching Dr Feingold's treatment. In the UK groups also started and the HACSG has adapted the diet for its own use.
Essential Fatty Acids
Following on from Bunday's groundbreaking work, considerable evidence is accumulating that deficiencies in the body's reserve or production of EFAs is a major contributory factor in a range of interrelated childhood disorders, including ADHD, dyslexia, asthma, allergies and even autism, and that EFA supplementation is valuable in a significant number of cases (Richardson AJ, Ross MA. Prostaglandins Leucotrienes and Essential Fatty Acids 2000;63(1-2):1-9). The overlap between ADHD and, for example, dyslexia is around 30-50 percent.
Fatty acids play an essential role in brain structure and function. Two of them -- arachidonic acid (AA) and docosahexanoic acid (DHA) -- play a major role in the brain and eye, constituting 20 percent of the dry weight of the brain and over 30 percent of the retina. Two others -- eicosapentaenoic acid (EPA) and dihomogamma linolenic acid (DGLA) -- are crucial for normal brain development but play a more minor structural role.
The absolutely essential fatty acids that cannot be synthesised by the body and therefore must be supplied in the diet, are linoleic acid (Omega-6 series, to which DGLA and AA belong) and alpha-linolenic acid (Omega-3 series, to which EPA and DHA belong). Both AA and DHA are termed longer chain polyunsaturated fatty acids (LC-PUFAs) and can usually be synthesised from their EFA precursors. The latter are critically important as precursors of a complex group of highly biologically active compounds including prostanoids (prostaglandins, thromboxanes and prostacyclins among others) and leukotrienes. These compounds perform numerous regulatory functions in the brain and the rest of the body.
Dr Alexandra Richardson (Physiology Lab, Oxford) and BK Puri (MRI Unit, Imperial College), in their important paper summarising the evidence ('The potential role of fatty acids in attention deficit/hyperactivity disorder' PLEFA 2000;63(1-2):79-87), state:
'EFA metabolism can influence many aspects of brain development, including neuronal migration, axonal and dendritic growth, and the creation, remodelling and pruning of synaptic connections (Crawford MA. in: Bazan NG. ed. Neurobiology of Essential Fatty Acids. NY: Plenum, 1992: 307-14).
'Animal studies have shown that both neural integrity and function can be permanently disrupted by deficits of omega-6 and omega-3 fatty acids during fetal and neonatal development (Yamamoto N et al. J Lipid Res 1987;28:144-51; Neuringer M et al. Annu Rev Nutr 1988;8:517-41; Bourre J-M et al. J Nutr 1989;119:1880-91). While both Omega-6 and Omega-3 fatty acids are required, the Omega-3 fatty acids such as DHA appear to play a special role in highly active sites such as synapses and photoreceptors, and deficiencies have particularly been linked to visual and cognitive deficits (Neuringer N at al. J Pediatr 1994;125:S39-47; Proc Natl Acad Sci USA 1986;83:4021-5).'
Research by M Makrides and co-workers has shown that infants may benefit considerably from the LC-PUFAs naturally present in breast milk but which are absent from many formula feeds (Lancet 1995;345;1463-8).
Although adequate supplies of EFAs are necessary throughout development and adult life to maintain normal function - and may be available - it is the conversion of the primary linoleic acid and alpha-linolenic acid into their LC-PUFA derivatives that is crucial for proper brain function.
Unfortunately, a number of factors can interfere with the conversion of these parent EFAs to their respective LC-PUFAs, including:
- Saturated or hydrogenated fats
- Deficiency of vitamin and/or mineral co-factors (especially zinc deficiency)
- Excessive alcohol
- Stress hormones
- Diabetes, eczema, asthma, or other allergic conditions.
Thus, even if the diet contains sufficient EFAs, the child or adult may not receive adequate LC-PUFAs due to deficiencies in conversion. In addition, individuals differ in their genetic constitutional ability to facilitate this conversion.
All the above, as well as disease factors, suggest the potential benefit of a dietary supplement of the preformed LC-PUFAs.
Features of EFA deficiency
The higher ratio of boys to girls with ADHD is well accepted and varies from 2:1 to 10:1 (Szatmari P et al. J Child Psychol Psychiatry 1989;30:219-30). This makes sense if ADHD is primarily a deficiency disease of EFAs since males are more vulnerable than females to LC-PUFA deficiency (Biochem Arch 1990;6:47-54).
The same excess male numbers are also found in other developmental disorders clinically associated with ADHD, including dyslexia and dyspraxia ( Am J Clin Nutr 2000;71(suppl 1):3235-65; Richardson AJ, Ross M. op cit, 2000).
An excess of minor physical abnormalities, such as abnormal palm creases, is associated with ADHD (Quinn PO et al. Pediatrics 1974;53:742-7) and EFAs, phospholipids and their metabolites play important roles in the cell abnormalities likely to underlie them (Hughes DA et al. J Nutr 1996;126:603-10).
Hyperactive children have also been found to have more chronic health problems, such as asthma or allergies, than normal children (Hartsough CS et al. Am J Orthopsychiatry 1985;55:190-210).
Children with ADHD have been found to have a higher incidence of sleeping problems than normal children: difficulty settling, waking in the night and over-tiredness in the morning (Trommer BL et al. Ann Neurol 1988;24:325). PUFAs play a major role in the control of sleep mechanisms and directly affect the structure of neuronal membranes and indirectly affect the dynamics of complex lipids, prostaglandins, neurotransmitters, amino acids and interleukins that are required for the initiation and maintenance of normal sleep (Yehuda S et al. Med Hypotheses 1998;50:139-45).
ADHD children exhibit more physical complaints than do normal children, including stomach aches, headaches, proneness to infections and general malaise with no obvious cause. In one study, 24 percent of ADHD boys and 35 percent of girls between 12 and 16 years of age fulfilled the criteria for somatization disorder (Szatmari P et al. 1989, op.cit).
Because fatty acids and their derivatives play a critical role in regulating immune and digestive functions (Alexander JW. Nutrition 1998;14:627-33), EFA deficiency is known to contribute to general health problems such as proneness to infections and digestive and related disorders.
Symptoms of depression, anxiety and low self-esteem are typical in ADHD, which is associated with other behavioural and emotional disorders. Up to 44 percent of sufferers have at least one other psychiatric disorder (Szatmari P et al. 1989, op cit).
There is increasing evidence is appearing that Omega-3 fatty acid deficiency may be important in depression (Hibbeln JR. Lancet 1998;351:1213; Peet M at al. Biol Psychiatry 1998;43:315-19). A recent double-blind, placebo-controlled study has shown the benefits of omega-3 fatty acids on the short-term course of illness in bipolar disorder (Stoll AI et al. Arch Gen Psychiatry 1999;56:407-12).
Poor motor coordination is frequently observed in those with ADHD and, similarly, 'soft' neurological signs, such as motor overflow movements, are also relatively common (Denckla MB et al. Arch Neurol 1978;42:228-31). Movement disorders in the general population are associated with deficiencies in LC-PUFAs (Nilsson A et al. PLEFA 1996;55:83-7) and thus poor motor coordination would be consistent with a lack of fatty acids.
The observed overlap of ADHD with dyslexia appears to be stronger for attentional disorder without overt hyperactivity than for the mainly hyperkinetic form (Dykman RA, Ackerman PT. J Learn Disabil 1991;24:96-103). The shared features include particular problems in specific aspects of visual and cognitive function (Conners CK in: Ravlidis G ed. Perspectives on Dyslexia Vol 1. Wiley, Chichester, 1990; 163-95). Deficiency in fatty acids has been proposed as contributing to dyslexia and there is growing evidence that supplementation can help alleviate aspects of the disorder (Stordy BJ. 2000, op cit).
Evidence for low Fatty Acids
In an early study, Michell and colleagues found lower plasma levels of DGLA, AA and DHA in 44 ADHD children compared with 45 matched controls (Clin Pediatr 1987;26:406-11). He also found that significantly more of 48 ADHD children compared with 49 age- and sex-matched controls suffered from polydypsia (chronic thirst) and polyuria (excessive urination), as well as health problems and language, learning and reading difficulties.
More recently, studies at Purdue University have provided further confirmation of abnormal fatty acid metabolism in ADHD. A team led by Stevens (Am J Clin Nutr 1995;62:761-8) found that, compared with 43 normal controls, 53 ADHD boys:
- were less likely to have been breast-fed (breast milk contains the preformed LC-PUFAs such as AA and DHA, whereas most formula does not);
- were more likely to suffer from allergies and other health problems (already known to be linked with EFA deficiency);
- showed clinical signs of EFA deficiency (excessive thirst, frequent urination, dry skin and hair, and soft or brittle nails);
- had reduced blood levels of certain LC-PUFAs (especially AA, EPA and DHA) but not their EFA precursors;
- had an adequate dietary intake of the EFA precursors.
The results support the hypothesis that EFA abnormalities are related to ADHD, and that the problem lies in the conversion of EFAs to LC-PUFAs. Some 40 percent of ADHD children had a raised frequency of clinical fatty acid deficiency signs compared with only 9 percent of controls.
Stevens and his team have also shown that both clinical signs and blood biochemical indices of fatty acid deficiency were significantly associated with the severity of reported behaviour problems and the incidence of learning and health problems (Stevens LJ et al. Physiol Behav 1996;59:915-20).
Another team, (Bekaroglu M et al. J Child Psychol Psychiatry 1996;37:225-7) found that the mean serum free fatty acid level in 48 ADHD children was significantly lower than in 45 matched controls. A further, significant correlation was found between zinc and free fatty acid levels in the ADHD children.
Early studies of GLA supplementation showed only equivocal or modest benefits (Arnold LE et al. Biol Psychiatry 1989;25:222-8). This was probably because, as Richardson and Puri (PLEFA 2000, op cit) suggest, omega-3 -- rather than omega-6 -- deficiency is more relevant in ADHD, and the studies did not last long enough to show any effects. Recent research indicates that LC-PUFA levels in the brain may take up to 3 months to recover from a chronic deficiency state (Bourre J-M et al. PLEFA 1993;4:171-80), and this must been taken into account in future studies.
At a National Institutes of Health Workshop on omega-3 essential fatty acids and psychiatry disorders held in Bethesda, Maryland, in September 2-3, 1998, JR Burgess (1998), from the Purdue team, presented preliminary results of a double-blind trial with ADHD children with clinical signs of fatty acid deficiency. They found that supplementation with a combination of DHA, EPA, AA and DGLA (weighted in favour of the n-3 fatty acids) successfully changed the blood fatty acid profile of ADHD children, and reduced ADHD symptoms.
However, another double-blind trial presented by R Voight at the same NIH workshop (Voight R. NIH: Bethesda, 1998) showed no benefits from supplementing with pure DHA. Richardson and Puri (p.84) suggest that one reason may be that DHA alone is ineffective and that other fatty acids, especially EPA, may account for the Purdue study's positive findings. They also point to the differences in subject selection; the Purdue study selected children based on prior indications of fatty acid deficiency, while no such pre-treatment indices were used in the Voight study, which excluded children with any other disorders to ensure that the sample comprised only 'pure' ADHD diagnoses.
To investigate the importance of EPA, Richardson is currently involved in a study of the effects of supplementing ADHD children with omega 3 fish oils.
Putting Nutrition First
The work of researchers like Dr Alexandra Richardson and Dr Neil Ward point irrefutably to two prime causes of the symptoms associated with ADHD. There is no question that there is a paucity of evidence for any long-term benefit from MPH; serious side effects are common, and its use in minors correlates with later stimulant abuse in adulthood (Lambert N, Hartsough C. J Learn Disabil 1998;31:533-44
It seems only common sense first to assess the nutritional status and heavy metal burden of any child suspected of ADHD, to correct it and to observe any improvements in behaviour before considering any highly potent drug therapy. Let MPH advocates remember Hippocrates' primary command: 'First, do no harm.' He might have added: 'Especially to children'.
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