Why do some people with narcolepsy crave sweet foods?

It all started on the Narcolepsy UK forum; a member was discussing how they craved sweet things on a regular basis and wondered why. The general consensus that came back was that craving sweet things was simply your body craving a stimulant to help it stay awake; but could it really be that simple? Well of course, this being narcolepsy the answer had to be no.

To start at the beginning with orexin, as most things do with narcolepsy. We use the term orexin but it is also known as hypocretin. Two groups were studying rat brains completely independently and within weeks of each other they both discovered the same compound. One group called it orexin, from the Greek meaning appetite while the other group called it hypocretin because it is produced in the hypothalamus and has a slight similarity to secretin. (Secretin is a hormone found in the gut). In the entire brain only between 20,000 and 40,000 neurons produce orexin out of a total of perhaps 100 billion.

Orexin is something called a neurotransmitter, a chemical produced by the body; usually in the brain (but not always for instance 90% of serotonin production occurs in the intestines) that transmits a signal from the end of the neuron to the target cell. This signal tells the cell to do something and with orexin that something was thought to be wake up. However, researchers have discovered there is far more to orexin than that. Over the last four years they have found that orexin has a role to play in the regulation of arousal, appetite, production of brown fat, the ability to process risk, keeping the body at an even temperature and (through stimulation of Substance P) how you experience pain. As researchers review orexin there is little doubt that this small but crucial neurotransmitter will be found to impact on other areas as well.

So we now know that orexin stimulates the appetite, is that why people with narcolepsy crave sweet foods? Well possibly but it isn’t the full answer. Orexin increases the appetite and not just the appetite for sweet foods; so while the desire to eat is increased the craving for sweet food isn’t. Of course orexin levels are significantly reduced in narcolepsy so if anything the appetite should be suppressed not increased.

In people with normal orexin levels, a hormone called leptin is produced by fat cells and acts as a sort of counter balance to orexin. The more fat cells you have the more leptin is produced and leptin naturally inhibits production of orexin; so leptin is one of the ways that the body tries to control appetite and weight. Leptin is produced even if you have reduced (or no) orexin so once again the more fat you have the less hungry you should feel. Of course with no or little orexin present, leptin will have nothing to react with and so your appetite might not be as well controlled.

However there is another factor produced by the stomach called ghrelin that might hold one of the keys to the simple question asked at the start. Ghrelin is an amino acid hunger stimulating peptide that is activated by the stomach just before you start your meal and it strongly increases the desire to eat. While orexin production is reduced by leptin it is completely the reverse with ghrelin which stimulates orexin production. So is the body, sensing it is short of orexin, increasing ghrelin production in the hope of stimulating the production of orexin? It sounds plausible and could certainly be one of the explanations as to why people with narcolepsy gain weight, but, we just don’t know. Many areas of narcolepsy need to be researched and this is just one of them; it’s an interesting hypothesis but that is all it is for the moment and it does not answer why people with narcolepsy crave sweet foods.

Which takes us to glucose; the first paper that reported glucose could inhibit orexin production was back in 2006 (Burdakov et al. Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose. Neuron. 2006; 50:711-22.). This showed that high glucose levels reduced orexin production so once again if anything, people with narcolepsy should find that their body steers them away from sweet things and not heads them to it. Then in 2011 a team at Cambridge produced a paper (Venner et al Paradoxical regulation of sugar sensing. Journal of Physiology. 2011; 589: 5701-8) confirming the 2006 results but showing it wasn’t that easy. They found that while orexin neurons could be blocked by elevated glucose they could also be increased by hypoglycaemia and that not all energy-related molecules reduced orexin production; pyruvate and lactate, can stop glucose from blocking orexin neurons. Pyruvate is formed in the body from metabolic procesees and is also found in apples, cheese, beer and red wine while lactate is of course found mainly in dairy products.

So, orexin neurons only ‘see' glucose changes when the levels of other energy molecules are low, whereas high energy levels can stop glucose from regulating orexin cells. That might be one of the answers as to why sugar is craved in narcolepsy; if you have a high energy uptake, as found in sweet things, it can actually stop the glucose from preventing orexin production.

Glucose sounded interesting and I decided to dig a bit further – in fact back to 1959 where I discovered the first report of a trial with narcoleptic patients and glucose. Schneider and Smith reported (Narcolepsy and Hypoglycaemia. J Ment Sci. 1959; 105: 163-70.) that patients who were given glucose in a drip promptly returned to drowsiness after administration. A very good, but small trial followed in 1994 (Bruck et al. Sleepiness after Glucose in Narcolepsy. Journal of Sleep Research. 1994; 3: 171-79) which again confirmed the Smith paper. The results showed that those with narcolepsy were not made more awake by glucose but felt more tired, went to sleep quicker and 11 out of 12 showed increased REM activity. At the time (and this was 4 years before orexin had been discovered) the findings were discussed in relation to serotonin synthesis, basal sleepiness and possible irregularities in the action of insulin.

Let’s also look at hypoglycaemia, which as we have seen can increase orexin production in people without narcolepsy. What is hypoglycaemia? It’s a condition that occurs when your blood sugar (glucose) is too low; blood sugar below 3.9 mmol/L is considered low and can harm you. It can occur if your body’s sugar is used up too quickly or glucose is released into your bloodstream too slowly or too much insulin is released into the bloodstream. When people - any people - are hypoglycaemic not only can they feel sleepy they can crave carbohydrates such as sugar. I can find no modern paper on hypoglycaemia and narcolepsy, which is surprising but must indicate this is an area that does not interest researchers.

What does all this tell us about why people with narcolepsy often crave sweet things?

We have seen that an increase of glucose, as found in sweet, sugary drinks and snacks could be helpful to people with narcolepsy in getting to sleep; and once asleep improving your REM sleep. If you have found that sweet things help you sleep this could well become part of your night time ritual and then it’s difficult to break away from. As it has worked before it almost becomes necessary in a subliminal way to do it again.
If you still have some orexin production going on, which many people with narcolepsy do, needing to eat sweet things could be your body trying to trick the orexin production areas to keep pumping the stuff out even though you are eating.

Then of course, if you have been asleep or resting for several hours and have not taken regular food or drink it could be that your blood sugar is low - you are hypoglycaemic. As this form of hypoglycaemia could again trick your body into producing orexin and every bit of orexin helps, you might even feel better, for a short time, with hypoglycaemia and so you either subliminally or deliberately reduce your food intake. When you then start to “crash” from lack of blood sugar your body craves what it needs – more glucose.

Or of course it could be what we began with; you use sweet things as stimulant to keep awake.

This small report has taken a long time to write and if I had hoped to get some concrete answers at the end of it I should have known better. This is narcolepsy after all! What I have been reminded is how many people there are out in the web, most well meaning, who try to peddle cures for narcolepsy through supplements and diets. I would love to say that some of them work and I do believe that some can help narcolepsy side effects. Several studies have shown that a diet low in carbohydrates/high in protein can help the symptoms of narcolepsy. The use of amino acids as either a supplement or through eating more egg whites and green vegetables also seems to improve the symptoms of narcolepsy. As does eating fruit in general and drinking cherry juice in particular. All of these help but none of them cure, or claim to cure narcolepsy. Perhaps to this short list we need to add, taking a sugary snack before bed time!
 

John Cherry

(Added to website 6th June 2012)