Catch me if you can

Before my foray into the world of celebrities I was talking about babies, children and the effect that illness can have on their metabolism. I have also alluded to something called catch up growth and the fact that it might be important for the overall risk of obesity and chronic disease.

What is catch up growth? The medical dictionary defines it as:

“…an acceleration of the growth rate following a period of growth retardation caused by a secondary deficiency, such as acute malnutrition or severe illness…”

The easiest way to track catch up growth in visual form (and you know that I like my visuals) is on growth charts. Children tend to follow an individual growth curve, predetermined largely by genetics, and this phenomenon is called “the canalisation of growth”. As we have established in the previous post, an illness or or a period of malnutrition may result in falling off the curve. Catch up growth is the body’s attempt to get back onto the original curve.

Growth curve flattening and fall (example only)

Accelerated growth during recovery phase

It has been known for quite a long time from observational studies that babies and children who undergo a period of catch up growth seem to be at higher risk for obesity and diabetes later in life. This was also observed in children born small for gestational age (SGA),  which is an indirect indicator of fetal malnutrition. Similar phenomenon was noted in children growing up in famines (the Dutch famine study) and the survivors of the Leningrad blockade in the WW2.

Studies conducted in the 60’s and 70’s looked further into the energy metabolism of catch up growth. They showed that the rate of growth in these children is astonishingly up to 15-20 times the rate of normal pattern. Moreover, this period was accompanied by both increase in appetite and increase in BMR in the order of 4-5 times the controls. It seems that when children were fed ad libitum they spontaneously increased their food intake to ensure their bodies get back on the curve. As their weight approached the expected measure for height their appetite would decrease back to normal levels.

Another interesting observation made around 1980 was that children do not regain lean body mass at the same rate as they lose it. Muscle recovery lags behind the recovery of fat tissue even when children regain their weight and get back on their growth curve. As one of the studies frames it:

“The impressive gains in weight made by recovering malnourished infants are largely fat; reconstitution of lean tissue does not occur equally well at all rates of weight gain.”

Let’s go back to some visuals or rather my illustration of the above.

Body composition changes during illness and recovery

The greater degree of the initial weight loss, the more unbalanced the pattern of catch up growth.

Later research started to elucidate the mechanism by how this imbalance occurs. Several studies have identified that the phenomenon of catch up fat is accompanied by hyperinsulinaemia, relative insulin resistance in skeletal muscles and hyperresponsiveness to insulin in adipose tissue.

Basically, when the child is recovering from a period of malnutrition their bodies produce more insulin for the same amount of glucose. Their muscles “shut down” the insulin gates and their fat tissue opens the gates wide so that glucose is shuttled away from the muscles and into fat.

Some of the more recent studies have tried to explain this phenomenon using terms like “thrifty gene”. Since no such gene has yet been identified to my knowledge I’m a little unconvinced. What interests me however is whether this slightly worrying pattern is diet-dependent. In other words, what do you feed a sick malnourished child to prevent this from happening? Is there a single dietary cause? What did all these children in observational studies eat?

Looking for causes in cohort data is always a fruitless exercise and a reminder that we should use it to generate hypotheses only. Randomised controlled studies on actual babies are obviously out of the question, I doubt there is an ethics committee on earth which would agree to withholding food from children and then watch them lose and then regain weight on various dietary regimens. There are always rats but they have an obvious disadvantage of being…well, rats.

One zealous study examined the rats undergoing catch up growth after semi-starvation. Those re-fed a high-fat diet were found to have more hypinsulinaemia, higher fat deposition and lower metabolic rate than the rats fed a low-fat diet. Both re-fed groups had worse metabolic derangement compared to controls. A closer attention to the high-fat diet tells you that the rats were fed 1:1 corn oil:lard mixture as 50% of their diet. What does it tell you? That it’s not a good idea to feed rats 25% of their diet as corn oil. Not much else really. It also makes it clear that both re-feeding diets resulted in higher insulin response to the same glucose load, higher adiposity, lower thermogenesis and other markers of disordered metabolism.

So we are back to generating hypotheses.

Recent developments implicate a group of messengers called IGFs, insulin-like growth factors. A series of experiments on none other than zebrafish showed that low cell oxygen level as would occur in malnutrition or disease can disrupt IGF signalling which activated the MAP kinase pathway, necessary for growth. Restoring oxygen to the tissues did not always result in full system reboot. Pathways other than MAP kinase may be activated which could explain the different growth pattern. Sigh… let’s wait for the zebrafish to give us the answer.

While you are digesting all of this info I will put together my take on some of these fascinating issues. Of course, I could be the only one who actually finds this stuff so intriguing and you might be going about your day without giving the concept of catch up growth a second thought. But I reckon some of this might still apply to you whether you are a determined bachelor or a mother of four. What if you were the one who had a prolonged illness at some point in your childhood? What if this pattern of metabolic disregulation also applies to the yo-yo dieters amongst us? Aha, now you are thinking about this.

Look out for my summary post on child metabolism in the next couple of days.

More reading:

Ashworth A, Milward DJ, Catch up growth in children (1986) Nutrition Reviews 44(5):157-163

Jackson AA, Wootton SA, The energy requirement of growth and catch up growth, Proceedings of an I/D/E/C/G Workshop held in Cambridge, USA 1989

Dulloo AG et al, Pathways from weight fluctuations to metabolic diseases: focus on maladaptive thermogenesis during catch-up fat (2002) International Journal of Obesity 26(S2): S46-S57

Ong KKL et al, Association between postnatal catch-up growth and obesity in childhood: prospective cohort study (2000) BMJ 320:7240

 

 

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Down the slippery slide we go!

J.Waterhouse "A sick child brought into the Temple of Aesculapius" 1877

Continuing from my last post about metabolism in babies and children, today I will address what happens when a child goes through a period of inadequate food intake.

Viral or bacterial infections, prolonged hospital stay and chronic disease are some of the common causes of temporary malnourishment in Western children. Frank underfeeding is fairly rare though it still happens in certain extreme dietary lifestyles. While there are definitely differences between chronic malnutrition (the kind we associate with “the starving children in Africa”) and a week-long diarrhoeal illness in a typical Australian child, there are many similarities.

A few older studies (they weren’t too hampered by ethical considerations in those days) examined underfeeding in babies and children in some detail trying to establish how the body copes with the lack of energy and nutrients.

If you remember from the previous post, energy intake in children accounts for their BMR (basal metabolic rate), activity and growth.

Intake = BMR + Activity + Growth

As it turns out, the body puts a different priority on each of these components. Survival (BMR) comes first followed by Growth and then Activity. As a consequence, a malnourished child will first decrease activity levels.

If reducing energy expenditure does not compensate for inadequate intake then growth becomes affected. Within growth 2 parameters are easily measured: height (length in infants) and weight, both can be tracked along growth centiles on standard growth charts. A prolonged illness might result in the slowing of weight gain which will be reflected in drop down a centile. Weight loss comes both from fat loss and muscle loss. While the organs are relatively protected in minor illness, the muscle mass is not.  Catabolism (breakdown) of muscle tissues has been reported even after measles immunisations and asymptomatic Q fever.

A profoundly malnourished child will also slow their height velocity possibly resulting in stunted growth.  All of the above will happen way before the metabolic rate of individual organs is affected.

Sequence of metabolic events in malnutrition in childhood

Reduction in activity in a malnourished infant may be subtle to the outside observer. The child does not necessarily lie motionless and exhausted in her cot but they might be less vigorous and inquisitive. An interesting study was conducted back in 1979 in a Mexican village. The investigators followed two groups of children: one was given supplementation of vitamins, minerals, strained foods and milk (in fact the diets of their mothers were supplemented in pregnancy as well), the other group was not. Supplemented babies were more active, cried less, spent more time out of their cribs. In one of the experiments 2 year olds were taken out onto a 3 x 3 quadrangle and their movements recorded for 10 minutes. Investigators recorded the movements of well-fed and malnourished infants. Some toys were placed in one end, their caregiver and two observers at opposite ends.

This is a tracing of the movements of a control child (no supplementation):

Source: Chavez and Martinez 1979

This is a tracing made by a supplemented child:

Whoa, somebody went a little crazy! Obviously the results could be related to both quality and quantity of the food given, better development in better fed infants, an uncertain deficiency in controls or some other factor. Nevertheless it is clear that malnutrition can affect the physical activity of children. One of the first questions a parent is asked by a pediatrician or a general practitioner is: “Is your baby happy and active?” This graph makes it clear why.

Anorexia, or loss of appetite, is something that most parents witness in a sick child. Spontaneous decrease in food intake is well described in scientific literature. What can be simpler: a sick child doesn’t feel like eating and loses weight as a result? However, while anorexia accounts for some of the weight loss, it does not explain all of it.

As I have mentioned before, children tend to lose muscle mass in addition to fat loss during illness. Muscle wasting, the two words that terrify any self-respected gym junkie, is a costly exercise in a child. Body composition is notoriously hard to measure in infants but we know that adipose tissue in 2 year olds can measure between 20-25%. So why don’t the children use their soft cushioning for energy when sick? As it turns out being ill makes it harder for the body to access fat stores. The signals from body’s own hormones and the activation of the immune system causes a switch to protein catabolism and utilisation of amino acids stored in the muscle for gluconeogenesis (creating glucose in the liver for release into the bloodstream).

Another mechanism by which acute disease contributes to the loss of muscle mass is the paradoxical increase in BMR, or hypermetabolism. Mechanisms of this are not entirely clear but it has been recorded across many studies. One of the main suspects is fever. The often quoted figure is the 13% raise in BMR for every 1 degree Celsius above 37° (It comes from an old study by Dubois, 1938, unfortunately I do not have a full text). However, these mechanisms cannot compensate for muscle wasting and decreased organ metabolic rate in chronic active disease and profound malnutrition. Protein can also be lost directly from the gastrointestinal tract via the process called protein-losing enteropathy  due to a variety of infectious, inflammatory or congenital causes.

It may be helpful to think of energy status in malnutrition and disease as a balance between energy conservation and energy loss. The adaptive mechanisms that the body tries to use fail in the face of a serious and/or prolonged illness resulting in negative energy balance.

Energy balance in response to illness

So let’s apply some of these factors to a hypothetical situation: an otherwise healthy 18 month old catches a nasty gastrointestinal bug, like Campylobacter, at his playgroup.

The first sign that something is wrong might be a slight decrease in activity. Vomiting and diarrhoea, energy-draining processes by themselves, prevent nutrient absorption.  Appetite decreases and the actual food intake may stop altogether. Negative energy balance kicks off a conservation response and the child’s activity reduces even more. If the episode is complicated by high fever you can expect BMR to rise slightly. Reduced activity will only be able to compensate the energy deficit up to a point. Laying down new tissues for growth has already come to a halt. By this stage the body may start to break down muscle for glucose and fat stores for energy. The longer this infection hangs around the more muscle is wasted. BMR starts to reduce due to the loss of fat free mass. After a week or two of being unwell you have on your hands a lethargic possibly dehydrated child, with reduced fat and muscle mass and a reduced appetite.

If the adverse stimulus (=infection in this case) is not removed the road to chronic malnutrition with subsequent growth stunting and reduced organ metabolic rate continues. The resolution of infection sends a powerful recovery signal and catch up growth begins.

However, catch up growth pattern is not the same as the normal growth. After taking a step back, the body has to leap 2 steps forward to get back on track. And it seems to have some trouble doing that. In my next post I’ll discuss the catch up growth and how it’s linked to obesity.

If you have children of your own I apologise if this post was a little unsettling. When your baby is unwell the last thing you want is a little paranoid voice in your head whispering about the inevitable lean body mass loss etc. I will discuss my ideas about the optimal nutritional strategies for recovery a little later, I promise.

More reading:

Scrimshaw NS, Energy cost of communicable diseases in infancy and childhoodProceedings of an I/D/E/C/G Workshop held in Cambridge, USA November 14 to 17, 1989

Wiskin AE et al Energy expenditure, nutrition and growth Arch Dis Child 2011;96:567-572

Veldhuis JD et al Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocrine Reviews 2005;26(1):114-146

Beisel WR Magnitude of the host nutritional responses to infection, American Journal of Clinical Nutrition 1977;30(8):1236-1247

Energy vampires and other matters

In my last post I talked about the inconsistencies and often the sheer stupidity of some of the nutritional advice we hear on a daily basis. One of the readers made a comment “I don’t understand the point she is trying to make”. Well, actually I’m not trying to send a big message here. My blog is where I write about what I see, comment on it (yes, sarcasm is my way of coping with some of the rubbish) and leave you to make up your own mind. Occasionally I throw a bit of science so you can see where I’m coming from. I do not spend hours doing an exhaustive literature search in Medline (I don’t have that luxury) but I’ve accumulated my fair share of information in the last 8 years of studying science and medicine and especially in the last year of learning about nutrition in particular.  If you see a study that supports some of the things here feel free to send it my way. Ditto if you feel it directly contradicts it.

Anyway let’s get into it. Today we are talking about metabolism in children. This post will be an overview of the basics and probably quite dry and boring. I’ll try to throw in some graphs and cute baby pictures for those who like that kind of thing.

It's been a few years but she still licks her bowl

I love the topic of child nutrition for several reasons. First, I have one of those little people at home so I’m naturally interested in what to feed her. Second, I believe that what you put in your body in infancy and childhood (and possibly even before, in the womb) is going to directly affect your health and size in the future. Third (and favourite), when you talk about child and particularly baby nutrition you take away the so-called “gluttonous sloth” theory of obesity and disease.  It’s ludicrous to accuse a 1 year old of a lack of willpower and laziness, so we are left with the bare bones of nutrition. And more than ever how that little body self-regulates its own nutritional status.

Metabolism (n) – the chemical processes occurring within a living cell of organism that are necessary for maintenance of life.

The Free Dictionary by Farlex

In other words, metabolism is the way your body processes the nutrients you receive with food. It’s tempting to look at food as pure energy but as we know calorie is not just a calorie. Food provides both the energy and the building blocks: 2 components required by each cell to perform its own unique function. In an adult this means you need to take in enough nutrition to provide energy for metabolic processes necessary for pure survival  and also the materials for the continuous repair, regeneration, special circumstances (illness, pregnancy, muscle growth).

In children, one more component is added to the picture = growth. The food they eat has to supply enough energy for basic metabolic processes and activity, building blocks for daily repair and regeneration AND additional intake to allow for growth.

Intake = Basal Metabolic Rate + Activity + Growth

Growth does not just come from extra energy but from extra nutrients required to create/synthesise new tissues. This has a few implications which I want to discuss in more detail later.

What is physical growth? Seems a silly question as this is a phenomenon most of us are very familiar with. We also have an intuitive understanding that different tissues grow at different rates, which accounts for a changed body composition. The body shape transition from a chubby baby to a stocky toddler to a lean pre-teen to the sex-specific changes in adolescence and finally into adulthood is multi-dimensional with unique composition corresponding to each stage.

An average newborn with a weight of 3.0kg (6.6 bs) increases her own weight by over 300% to around 10kgs (22lbs) by the end of her first year. Her brain weight goes from 450-500g to over 1000g in the same period of time, a weight remarkably close to 1400g in an average adult.

If you look at babies’ body composition their perceived chubbiness turns out largely illusionary. The body fat measurements of a newborn average a very svelte 12-15%. The remainder is allocated a name of FFM = fat free mass which consists of organs, muscles, skeletal structure and extracellular fluid. In the table below you can see how body composition changes in the first 18 months: muscle mass and fat mass increase, extracellular fluid decreases. Organ weight increases in proportion to body weight in the first year of life therefore the relative percentage of brain, liver, heart and kidney remain similar.

Adapted from Holliday,1986. ECF = Extracellular Fluid

Basal Metabolic Rate (BMR) in babies is determined mainly by the metabolically active tissues of the brain, liver, kidneys and muscles. The brain activity of a newborn is estimated at a whopping 80% of her BMR, dropping to about 60% through the first year as activity increases and muscle becomes more metabolically relevant.  In addition to organs and muscles there is new evidence that some of the fat mass in babies and children is in form of BAT = brown adipose tissue which is more metabolically active and itself participates in energy expenditure. (Adults have some BAT too but in much smaller quantities).

Distribution of brain, liver and muscle metabolic rates as percentage of total BMR at different body weights (Holliday 1986)

So what have we learned so far?

The energy intake in babies and children has to account for their high relative BMR, allow for activity and also provide the energy for the process of synthesis of new tissues PLUS the energy that is deposited in new tissues.  Once again:

Intake = Basal Metabolic Rate + Activity + Growth *

*For science geeks, I have left out the Diet Induced Thermogenesis for the sake of simplicity and uncertain contribution to energy balance in children

It’s official. Babies and children are energy vampires. This might sound very daunting for the food providers, the parents.  How do you know how much to feed a child to ensure all these processes perform without a hitch? At the same time the growth of most infants follows a fairly predictable pattern. Whether they are breastfed on demand or formula fed by the hour, whether they are weaned onto rice cereal or meat, save for small variations in fat mass their FFM (fat free mass) will be very similar.

Lucky for us, parents, we do not have to hunt around for scientific papers estimating energy expenditure, calculate our child’s activity and measure out every spoonful. Under normal circumstances, babies seem to do quite well without science.

That is when everything goes well. What if it doesn’t? For the first time in human history we are way more concerned with OVERnutrition rather than UNDERnutrition. But it is probably too simplistic to completely separate these two. Next post I will look at malnutrition and the fascinating subject of catch-up growth and what it can teach us about childhood obesity.

More reading:

Veldhuis JD et al 2005 Endocrine control of body composition in infancy, childhood and puberty. Endocrine Reviews 26(1): 114-146

Activity, energy expenditure and energy requirements of infants and children, Proceedings of an IDECG workshop held in Campbridge, USA, 1989

Holliday 1986 Body composition and energy needs during growth. In: Human growth: a comprehensive treatise, 2nd ed. Plenum press, NY 1986

Calorie is a calorie is a calorie. Part I

What is a calorie? In the world of physics, a calorie is the amount of energy required to heat 1 gram of water by 1 degree. In nutritional terms, calories mean food energy, energy in turn signifies how much we burn and how much we store. Somewhere in the equation is the first law of thermodynamics, which is generally interpreted as: calories in must equal calories out. If we apply this law to human metabolism we get the conventional wisdom: to lose weight you need to eat less and exercise more. No-brainer, right?

Let’s explore these concepts in a little more detail. I am no physicist (I can just see my physics lecturer nod fervently to this statement). If I can slowly walk my subtle-as-a-sledgehammer brain through these abstract concepts, so can you.

Food calories

How is the caloric value of common foods determined?

The well-known 4,4,9 calorie values per 1 gram of carbs, protein and fat respectively, were first derived in the early 1900s by Wilbur Olin Atwater. He used a machine of his own invention, the respiration calorimeter, to measure the heat production of foods in the typical diet of the beginning of the 20th century. I would hazard a guess that our foods today are somewhat different to the ones Atwater happily incinerated in his lab. The unit “calorie” was used to measure the amount of heat energy released. Proteins, carbs, fats, alcohols, polyols and fibre were all allocated their average values and the rest is history. Apparently the use of Atwater system “has frequently been the cause of dispute, but no real alternatives have been proposed”.

Today most food manufacturers use the Atwater system to calculate the total calories in their product. Another less commonly used method is calorimetry, similar to Atwater’s experiments. The food in question is combusted with oxygen and the amount of heat energy generated is measured. Here is the first hiccup. Human bodies obviously do not “burn” food or generate that much heat. Getting really hot is a major problem for our brains as they tend to get delirious. Instead our bodies generate ATP, the carrier of energy required for all biochemical reactions in your body. Carbs, protein, fat, alcohol – all have the potential to generate ATP.

Why the potential? Because not every morsel that goes through your mouth is used for ATP production. Protein can be broken down to amino acids which can be used as energy. However, they are preferentially used up for cellular repair or the building of new proteins. So if your body is in the state of growth, illness, recovery from your latest unsuccessful attempt at a pull-up (guilty as charged), you might not be “burning” any of the protein that comes from your steak. In the same way, glucose can be used to replenish your glycogen stores in
the liver and skeletal muscles. So if your glycogen stores are empty after a workout, the glucose will be used preferentially to refill them. Fatty acids are used for building cellular membranes and cholesterol for hormones.

Basically, your body is not a furnace and your metabolism is not a ritual burning of a piece of cake. Biochemists have neatly summarised this process in the diagram below. I call it the WTF diagram.

A bit different from “fat=calorie in – calorie out”, don’t you think?

But can’t we average all these processes and come up with a number of food calories required for everyday function? What about Basal Metabolic Rate, the BMR? Someone somewhere has worked it out. I can google the formula! And once I know it, I can just subtract 500 calories daily and it will result in half a kilo loss per week, right?

The BMR story

A nerd in me is very attracted to this simple idea. Calculating an easily predictable weight loss value is so elegant. And knowing your own special number, your Basal Metabolic Rate, is almost empowering.

Harris-Benedict equation
The easiest way to do it is the Harris-Benedict equation suggested in 1919 (that’s before we knew about DNA). It estimates the strongest predictor of your BMR = your muscle mass, by taking into account your age (because older people always have less muscle), your sex (because women are always the weaker sex) and your weight (because your weight always indicates how muscle you carry).  I don’t know about you but I have a few issues with some of these assumptions.

DEXA scan
The next way to do it is to use the actual lean body mass measurement, either by DEXA scan or by the “fat scales”. I will not go in why the “fat scales” is a complete waste of your time and money. Let’s assume you do a DEXA, an x-ray imaging tool which will tell you your exact body composition. You also receive this charming picture. While it may tell you how much muscle you have (and diagnose osteoporosis, which was the initial application of this test), it won’t be able to tell if you are sick with pneumonia, if you are taking antidepressants, if you have  overactive thyroid, insulin resistance, phaeochromocytoma and a host of other things which will determine your own fuel utilisation rate, a.k.a what your body does with your food.

Because your metabolism is not regulated by your muscle cells.
It is regulated by hormones.

Thankfully, in the research world there are two ways to actually measure the metabolic processes which happen in an individual organism: indirect and direct calorimetry.

Indirect calorimetry
Most energy-generating pathways in the body require oxygen and result in the production of carbon dioxide (CO2) as a by-product. Therefore if I fit you with a special gas mask, make you breathe (this shouldn’t be too hard) and then measure the amount of oxygen in and CO2 out, I can get an estimate of how much ATP you are generating, and also how much fat vs glucose you are using for its production. This “metabolic monitoring” is also used in Intensive Care Units to work out the energy requirements of critically ill patients. It is obviously a very involved process. Nevertheless, here is a study which address the potential pitfalls of interpreting measurements without taking into account the hormonal environment.

Are you serious? I am breathing through a machine and you are still not a 100% sure how many calories I need???

Direct calorimetry
This is the final frontier, the golden standard. The description of this  process can be summarised in just a few words: “secure chamber”, “constant  temperature”, “air seal” and my favorite, “the panic button”. Yes, your whole body has to  be inside, sometimes for several days. A couple of problems: first, it only  measures your metabolic rate at that particular time. I hope we all agree that  metabolism is not a static number, multitude of variables can affect it from day  to day. The second problem is that it is a tad inconvenient.

So what are we left with? Helpful websites offer an easy formula to  calculate your BMR measurement, your TDEE (Total Daily Energy Expenditure)  measurement, your AUN (Another Useless Number) measurement. Then you subtract  500 calories (what a lovely even number) from your total, and that should give  you a 1/2-1 kg loss each week. Conveniently, this rate of weight loss seems to be fairly  similar no matter which diet/exercise regime you choose.

It might sound ridiculous that somebody might rely on a formula developed  in 1919 to estimate the BMR of an average healthy person under normal conditions  to apply in 2011 to an overweight individual. Followed by the advice to reduce their food intake by checking the caloric values, found by incinerating these foods under lab conditions. Finished by the recommendation to expend more energy by  exercise while checking the number of calories supposedly burned on a treadmill machine where you input your weight and sex.

In other words, the absolute number of calories is about as useful as knowing how much the loose change in your wallet weighs in poods. The units are  useless and how is it relevant to how much money is there anyway?

In part II I will discuss the application of ‘calories in = calories out’ to weight loss.