Issue 127 low protein diets in metabolic disorders an overview by NH Publishing Ltd

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LOW PROTEIN DIETS IN METABOLIC DISORDERS: AN OVERVIEW Suzanne Ford NSPKU Dietitian for Adults Suzanne Ford works as a Metabolic Dietitian for Adults at North Bristol NHS Trust. She has been a Dietitian for 21 years, with six of them working in Metabolic Disease.

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In this article, I will cover the principles of low protein diets, the nutritional and practical challenges posed and how metabolic dietitians and patients are collaborating to seek and share knowledge of good practice and develop the evidence base. In Metabolic Dietetics (and in healthcare in general) we can all expect to see more patients in the future with disorders needing low protein diets. In 2015, the newborn screening panel was expanded to include four additional metabolic disorders; so, the improved diagnosis and management will see higher numbers of patients surviving into adulthood. Low protein diets are a key feature of Metabolic Dietetics and there are two broad types: one is the safe protein diet which may be used in urea cycle disorders, organic academics etc, and the second is the exchange based diet for phenylketonuria, tyrosinaemia, homocysteinuria and isovaleric acidaemia. This requires commitment from the patients or families and knowledge, skill and clinical judgement from dietitians. In both these groups of diets, the evidence base and food analysis knowledge is incomplete and evolving. The aims of a low protein diet are to: • minimise the production of toxic metabolites; • supply all amino acids for any growth and development; • supply amino acids for basic tissue turnover; • minimise the release of any endogenous toxic metabolites caused by catabolism. SAFE PROTEIN DIET

WHO/FAO/UN 2007 Safe protein levels are given in age and gender

Table 1: WHO/FAO/UN 2007 Safe Protein levels Age

Intake g/kg bw /day

16y

0.84

17y

0.83

18y

0.82

>18y

0.83

specific grams per kilo of body weight. (Pregnancy and lactation have been omitted, as I will not cover those in this piece.) The amount of natural protein tolerated by patients with different disorders will vary dependent on the disorder itself and the individual's phenotype, i.e. the expression of the genetic mutation they have. In many cases, protein allowances are titrated up from infancy through childhood to adulthood, using a combination of prediction equations and biochemical monitoring in conjunction with nutritional intake analysis. Practices throughout UK metabolic centres and also European centres have been surveyed and published in the last five years and consensus clinical guidelines are under development, or have been published for metabolic disorders such as homocystinuria. The practices surveyed for low protein diet prescriptions focused on both the gram per kilo protein prescribed or used and also the use of essential amino acids (EAA). EAA are used to achieve normal growth and metabolic stability (if a particular amino acid

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CONDITIONS & DISORDERS Table 2: Table of Exchanges: amount of food providing one exchange or 1g of protein - a small sample Food

Tyr

Phe

Leu

Food

Tyr

Phe

Leu

Cows' milk

30ml

15ml

Jacket or boiled potatoes

50g

80g

60g

Single cream

30ml

40ml

20ml

Roast potatoes

35g

55g

45g

Double cream

60ml

35ml

Chips

25g

45g

35g

is rate limiting then muscle protein may be catabolism to release that amino acid, which could raise levels of the toxic metabolites). Prescription of amino acids is a difficult clinical decision to make, as it is likely to push up the overall nitrogen intake and risk pressure on the defective metabolic pathway, e.g. giving EAA in urea cycle disorders could raise ammonia levels - hyperammonaemia causes encephalopathy due to astrocyte (neurons) swelling. If EAA are given, ideally they would make up 20-30% of the total nitrogen requirement and would be taken in divided doses spread through the day for optimal assimilation. In the UK and Europe the safe protein intakes prescribed to patients ranged from 0.4g/ kg/d to 1.2g/kg/day and those surveyed said that they would base the prescription on metabolic stability (i.e. Number of recent decompensations), ammonia levels and qualitative amino acids in the blood (QAA). The natural protein choices in the diet should include sources of high biological value protein - this is challenging, as these are potentially concentrated sources of protein, i.e. portion sizes need careful judgement – however, this will give a better supply of all EAA than cereal protein for example. More work is needed for these types of diet, focusing in particular on adult patients who experience pregnancy and lactation and start to acquire comorbidities such as diabetes, hypertension, overweight and gallbladder disease. EXCHANGE BASED LOW PROTEIN DIETS

For more restrictive low protein diets, an exchange system may be used to teach patients how to constantly assess their own protein intake through the day and make food choices to fit a very precise protein prescription,

e.g. some adult patients with classical phenylketonuria may be on three exchanges per day, whereby an exchange equals 50mg phenylalanine or 1g protein. Thus, there is an exchange system for phenylalanine and also for tyrosine, leucine, methionine and lysine. Not all exchange systems are the same; for instance, the leucine system is for 100mg leucine. The foods which have been analysed for their amino acid content are usually analysed for all five of these amino acids and show that milk and creams have different acid contents, as do vegetables, etc. See Table 2 for a comparison of a small range of foods in the phe, tyr and leu exchange systems. Precision is needed - just being low protein and choosing low protein foods might not achieve metabolic control as having both too little or too many exchanges in a day can cause symptoms. Exchanges per day for adults typically range from six to 20 with some patients who have mild variants of the disorder having 20, 30 or maybe even 40 exchanges (quite unusual). The following are the different elements of a highly restricted, exchange system diet: • Exchange free foods (i.e. foods which can be eaten without counting for protein content). • Exchange Foods (those to count or weigh to provide small amounts of natural protein). • Foods to avoid (usually high protein foods such as meat, fish, eggs or cheese, also nuts and seeds). Some high protein foods might sometimes be used as exchange foods. • Low protein prescribable foods such as low protein bread, pasta, biscuits, crackers, cakes, milk substitute and flour mixes, or baking aids such as an egg replacer. • Protein substitute - commonly amino acids, there is a newly available glycomacropeptide.1 www.NHDmag.com August/September 2017 - Issue 127

CONDITIONS & DISORDERS Annual nutritional monitoring must include the following:3 • Three-day food diary demonstrating: - protein substitute use - the dose and timing, or Essential Amino Acids - use of any separate micronutrients - use of low protein prescribable foods - use of Emergency Regime including time off protein containing foods •

Bloods taken in (minimum) annual clinic: - Full blood count - Urea and electrolytes, liver function tests, bone profile - Serum B12, ferritin and folate - Serum vitamin D - Homocysteine - Methylmalonic acid - Qualitative amino acids - Sometimes zinc, selenium - Thyroid function tests if indicated and parathyroid hormone - Ammonia and glutamine in urea cycle disorders (ammonia must be put on ice)

•

Checking with patients if they attend GPs for intramuscular B12 injections.

•

Anthropometry: weight, height and BMI need to be measured and recorded.

•

For adults with bloodspots: monthly.

MONITORING FOR NUTRITIONAL AND CLINICAL EFFECTIVENESS ON A LOW PROTEIN DIET

Monitoring is vital - we know that adults on low protein diets may have insufficient micronutrients and perhaps protein, due to dwindling compliance with protein substitute in adolescence and early adulthood - yet they still restrict their natural protein intake,2 leading to protein deficiency and anaemias and various clinical and functional sequelae. LOW PROTEIN PRESCRIBABLE FOODS

These foods may comprise up to 50% of the Kcal intake of someone on a highly restricted protein diet and thus a large number of prescriptions each month may be required. The NSPKU have guidelines on the amounts - see www.nspku.org for further information. A survey of Scottish patients’ experiences of prescribable foods4 shows that patients appreciated these products: 97% said that they were important for management of the PKU diet; 89% said that the prescribable foods 36

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were important for phenylalanine control, satisfying appetite and improving diet variety. The sensory properties of these foods are well perceived by patients; however, if a product is discontinued, it is difficult for patients to easily find a similar prescribable alternative. Thus, product discontinuation can prove quite challenging for patients and families. Another challenge widely experienced is accessing prescribable foods easily and in a timely manner. Half of those surveyed by Cochrane et al4 had experienced comments on their prescription and 60% of the comments were negative. As the gluten-free food prescription system is out to consultation by NHS England, the author imagines this situation could worsen. Home deliveries have alleviated some of these issues, where home delivery is possible; however, some GPs even decline to allow home delivery and monthly scripts, for fear of companies overstocking patients’ homes with their products. The challenges anecdotally relayed are that community healthcare professionals perceive that these products are similar to glutenfree products and could be purchased easily in a supermarket. Other perceptions which are expressed are that whole families are consuming the prescribed foods, or that cakes and biscuits are luxury items which must not be paid for as part of NHS service. NEW FOODS IN SUPERMARKETS

NSPKU have funds which are used for amino acid analysis and the constantly evolving food industry means that new foods are always needing analysis. A good example of this are the hybrid vegetables such as kalettes which are a hybrid of kale and Brussels sprouts, both of which have some phenylalanine content which must be counted in the diet for people with PKU. A recent rise in the use and availability of coconut products in milk substitutes, yoghurts, puddings, ice creams etc has helped increase the variety of foods which are exchange free or very low in exchanges. SOURCES OF SUPPORT AND INFORMATION

We know from surveys that a low protein diet (with exchanges) takes carers of young children,

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