Type ‘What is GMP?” into a search engine and you’ll probably get reams of information on ‘Good Manufacturing Practice’ or ‘Good Medical Practice.’ Both very important but not what we’re thinking about in relation to PKU.

GMP is GlycoMacroPeptide

That is quite a mouthful so I’ll use the acronym. GMP is a protein which occurs naturally in cheese whey. “Great” you say, “but we can’t have cheese.” (Or “Grate,” you say, “but we camembert it.”)

Stick with me here because when GMP is extracted from cheese whey, “it is the only known dietary protein that is naturally free of Phe.” 1 Actually that same paper points out that is has a minimal amount of Phe - 5mg per gram of protein. Or 0.5g Phe in 100g of GMP. This is border-line free for people on the PKU diet. 2

So far so good, but what good is GMP beyond that?

Taste!

All of us on the PKU diet know how hard it can be to force down an unpleasant supplement after a tasty meal. Spare a thought for those making the supplement. To be useful in any way our medicine must contain some pretty foul tasting components. On a PKU study day in London last year the Nutricia product development team demonstrated this by asking delegates to mix their own ‘Amino acid supplements’ (pictured). The results were enough to make everyone present a little more grateful for the efforts put in by flavour developers.

All of the scientific trials I read for this article reported that the (human) participants found the improved flavour of GMP easier to consume. This is extremely important as the “Lifelong adherence to the PKU diet is very difficult, often resulting in poor compliance and the neuropsychological consequences” 3 of high Phe levels. If a medicine is palatable, it is far more likely that the patient will stick to the treatment.

Hunger and heartburn

I’ve been fairly lucky with my supplements in the past, but one of my current treatments does give me gastrointestinal problems fairly frequently. This can matter just as much as flavour. When a medicine makes you feel works, one is much less inclined to keep taking it no matter what the taste.

Trials to date suggest that GMP can lead to “improved gastrointestinal symptoms and less hunger.” 4Anecdotal evidence from both my home testing https://pigpen.page/new-chocolate-sphere/ and from my PKU community on twitter agrees with both of these claims.

Can it also mimic LNAA treatment and reduce brain & blood Phe?

All of the above is sounding pretty damned good, for most people it’s enough that a new supplement tastes better. But it’s looking like there might be even more benefits to using GMP over a synthesised amino acid supplement. Of most interest is a possibility of an effect similar to that attempted in LNAA (Large Neutral Amino Acid) treatments.

The mechanism of LNAA treatment is essentially that of competition. Phe is one of nine LNAA’s which all use the same ‘transporter’ to cross the blood-brain barrier. As Phe causes problems when it crosses this barrier, the theory goes that flooding these ‘transporters’ with other LNAA’s reduces the amount of Phe which crosses the barrier. This in turn dilutes the concentration of Phe in the brain and reduces the adverse effects. Obviously this is a very basic outline, you can read more about LNAA here - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992655/

It looks like GMP supplements might also have this competition effect, another plus to these exciting new treatments. “Studies in the PKU mouse model demonstrate that ingestion of GMP lowers Phe concentrations in blood, and to a greater extent in brain tissue, possibly through competitive inhibition of Phe transport across the blood–brain barrier due to the naturally occurring high concentration of LNAA in GMP.” 5

Finally, but just as important, one of the studies reported that the lower cost of making GMP means that the treatment might become a more viable option in poorer countries. 6 I confess I did not expect to be counting my blessings while researching for this article, but I am lucky to have been born in a country which has the expertise and resources to diagnose and treat PKU.

It seems appropriate to end on the call of scientists across the ages - More Data Required!

“Further research is required to investigate the long-term nutritional safety of GMP and its ability to reduce concentrations of phenylalanine in blood and brain and to improve compliance with the PKU diet.”7

  1. Nutritional management of PKU with glycomacropeptide from cheese whey. Ney, D.M. et al. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633220/ Accessed April 2019 ↩︎
  2. PKU Exchange Ready Reckoner. [] http://www.nspku.org/publications/publication/pku-exchange-ready-reckoner Accessed April 2019 ↩︎
  3. Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids. van Calcar, S.C. et al. https://academic.oup.com/ajcn/article/89/4/1068/4596723 Accessed April 2019
  4. Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial. Hey, D.M et al. https://academic.oup.com/ajcn/article/104/2/334/4668552 Accessed April 2019 ↩︎
  5. Nutritional management of PKU with glycomacropeptide from cheese whey. Ney, D.M. et al. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633220/ Accessed April 2019 ↩︎
  6. The Use of Glycomacropeptide in Dietary Management of Phenylketonuria. Zaki, O.K. et al.https://www.hindawi.com/journals/jnme/2016/2453027/ Accessed April 2019 ↩︎
  7. Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids. van Calcar, S.C. et al. https://academic.oup.com/ajcn/article/89/4/1068/4596723 Accessed April 2019