Anorexia and Bulimia: Closing points
by Emma Leigh
Impact on Physique:
A (brief) look at the effects on the STEROIDS and PEPTIDES
THIS is a major topic and I am unsure of where to start and the detail to cover…. But here be a brief overview…. The body is a finally tuned ‘mesh work’ of hormones and chemicals that are aimed at maintaining ‘the status quo’. And if we are generally thinking about what the body sets out to do – humans are, above all, aimed at ‘survival’. We like any other organism, aim to survive in order to ensure procreation for survival of the species. As such – If you decrease energy intake or increase energy output you create a situation which places ‘stress’ on the body, and you ‘rock the boat’. This is especially the case in females (substantially so) – with even small/ minor changes to energy balance seen to create very large compensatory changes to things such as appetite, reproductive hormones, and metabolism in general.
And some major alterations seen during anorexia and bulimia can be divided into three main areas:
- Leptin (the major hormone produced/ responding to adipose tissue/ energy stores)
- Some of the hypothalamic-pituitary hormones
- Some of the gastro-intestinal hormones
So… Let’s whip through these…
Leptin
- Made/ expressed mostly in (white) fat/ adipose… But it is also secreted from the hypothalamus & pituitary, skeletal muscle, the stomach, and the placenta and mammary tissue in preggo females
- It is thought to be secreted proportionally to the amount of energy stored in fat and it acts in the hypothalamus and a variety of peripheral organs to regulate homeostasis and reproduction. This includes thyroid and thyroid hormone conversion rates, cortisol/adrenal hormone secretion, gonadal hormones (sex hormones) and also growth hormone (and IGF-1).
- When fat stores are low, and Leptin decreases, it acts to decrease energy output and ‘slow down’ the body. It also switches off reproductive capacity
- Unsurprisingly, Leptin levels are low in those with AN and BN…. specifically:
- In anorexia: Serum and CNS Leptin concentrations are significantly reduced. Low body fat being the major determinant of the decreased serum Leptin.
- The ratio of free:bound Leptin changes – where free Leptin (thought to be the biologically active form) is relatively decreased with significantly higher proportions of bound Leptin. Thus, not only do you get decreased levels, but you get proportionally less ACTIVE form of Leptin too.
- In bulimia: Patients have significantly lower serum Leptin levels compared to weight/age-matched controls, but not as low as in patients with anorexia nervosa (probably related to higher bodyfat/weight). Leptin is also related to chronic binge disorder – being more significantly decreased in those with more chronic/ severe disease.
- Weight gain and normalization of eating patterns USUALLY leads to increases in serum leptin but may not restore NORMAL levels.
HP Axis Hormones
Thyroid Hormone
- Thyroid hormone is made in the thyroid gland in response to TSH (thyroid stimulating hormone) from the pituatry (which is stimulated by TRH from the hypothalamus)
- It is mainly released as T4 (mostly inactive) and converted into T3 (the active form) in the tissues
- It is a key regulator of metabolism in the body – relating to how ‘fast’ the cells of the body function
- It is seen to change in response to energy intake/ output, disease, stress etc.
- It is therefore not surprising that TSH, T4 and T3 are seen to decrease in Anorexia, with the low serum levels of T3 thought to be the result of impaired peripheral conversion of T4 to T3.
- Thyroid changes are thought to be related mostly to Leptin – and some evidence suggests that Leptin, when given to food-deprived healthy volunteers, can restore TSH pulsatility-changes. It should be noted that during refeeding of those suffering from LONG term starvation these changes often persist – with free T3/ T4 levels remaining low for prolonged periods.
Cortisol
- The ‘evil’ stress hormone – this is a hormone secreted by the adrenal glands in response to ACTH from the pituitary. It is seen to increase in states such as decreased blood glucose/starvation, illness or injury (plus many others).
- In anorexia the elevated cortisol levels have been suggested to be due to two things – the first is an increased secretion, but also it seems to ‘hang around’ for longer due to the decreased metabolism / excretion rate.
- Unlike TSH/ Thyroid hormone – Leptin given in replacement doses to food-deprived healthy volunteers does not alter the changes in cortisol (and in the renin-aldosterone system in the adrenals)
Growth Hormone (and IGF-1)
- Growth hormone is a hormone released from the pituitary and relates to the stimulation of ‘growth’
- This it does in a few ways: the most important being it’s direct action on the GHR (growth hormone receptor) that is found in a number of different tissues, and the second is via the stimulation of Insulin Like Growth Factor 1 and 2 (IGF-1 and IGF-2) from the liver.
- Growth hormone levels are seen to rise in many different situations – in those who are growing, low blood glucose/malnutrition, severe illness/catabolic states, malabsorption, liver disease, and diabetes mellitus (insulin dependent or type one), and some forms of physical activity.
- In Anorexia/ bulimia GH secretion is actually INCREASED – BUT there are two things that are also seen – the first is a reduced IGF-I concentrations and the second is a decrease in the peripheral GHR. This is believed to be a consequence of a malnutrition-induced peripheral GH resistance which alters tissue response, failure of IGF stimulation and an impairment of the negative IGF-I feedback action on GH secretion (circulating IGF-1 passing through the pituitary-hypothalamus usually influences the amount of GH released – but in AN you don’t get this feedback, and GH continues to be secreted).
- The increased circulating GH and decreased IGF results in negative body composition and metabolic changes which I will go into a little later.
- Lastly – The GH/IGF-I axis is generally restored by nutrition and weight gain.
Intestinal Hormones:
Insulin / Glucagon
- The pancreas, found in the upper abdomen, is involved two main functions:
1. Producing digestive enzymes to break down food; and
2. Producing the hormones insulin and glucagon to control sugar levels in your body.
- In a nut shell – when blood glucose goes up, the pancreas secretes insulin to increase uptake into muscles and other cells. When the blood glucose goes down the pancreas secretes glucagon which causes the body to mobilize endogenous fuels to raise blood glucose
- Although it seems illogical – Patients with anorexia nervosa frequently have impaired glucose tolerance
- This is associated with insulin resistance and an increased risk of cardiovascular pathology
- During recovery there is often a ‘reactive hypoglycemia’, which is where the body becomes more insulin sensitive, but still produces far too much insulin in relation to glucose feeding, and often those recovering will suffer from dips in their blood sugar after eating. This, like many other abnormalities, improves over the course of recovery.
Ghrelin
- Synthesized predominantly in the stomach and increases food intake
- Levels rise on fasting (with sharp peaks occurring just before each meal) and fall rapidly on feeding
- It is thought to cause short term hunger – so called ‘pre-meal hunger’, and leads to meal initiation and stimulation of GH
- It also plays a role in longer-term appetite and energy balance – with Ghrelin decreasing in response to chronic overfeeding (obesity) and increasing in chronic negative energy balance (exercise or anorexia nervosa). This means obese people usually have high plasma leptin they have low plasma Ghrelin where Anorexics have low Leptin and high Ghrelin.
- It should be noted that chronic EXOGENOUS administration leads to continuing overeating and weight gain
Peptide YY
- Secreted from the endocrine L cells of the small and large bowel
- Released into the circulation after meals
- Likely to be important in the everyday regulation of food intake and decreases food intake
Glucagon-like-peptide-1
- Glucagon-like-peptide 1 (GLP-1) is co-secreted with PYY in response to nutrients in the gut
- GLP-1 plays an additional role in enhancing insulin secretion and suppressing glucagon secretion after a meal
- It acts to increase plasma insulin levels and inhibits glucagon release
- It also decreases food intake, which is thought to be related to a decreased rate of gastric emptying
- GLP-1 concentrations are significantly higher in AN than in other ‘naturally thin’ individuals and may be related to the increased rate of satiety seen in anorexics
Cholecystokinin
- Inhibits feeding, stimulates pancreatic enzyme secretion and gallbladder contraction
- Peripheral CCK has a rapid & short-lived effect on feeding, (~20-30 mins) and mediates satiety
- CCK may play a role in longer-term energy regulation by synergizing the actions of leptin which may occur by CCK activating brain stem neurons that project to the hypothalamus combined with leptin’s direct hypothalamic actions
So – to put these together:
- Lower Leptin
- Decreased thyroid hormone
- Increased cortisol
- Increased Growth hormone but GH resistance and decreased IGF-1
- Decreased insulin response to feeding
- Higher basal Ghrelin
- Higher peptide YY and higher CCK
What does this mean in relation to body composition?
In anorexia – your bodyfat goes down initially. However, depending on the state of starvation and the degree of malnutrition, lean mass will eventually decrease and the patient is left with not much of anything. In Bulemia most people are at normal weight, and can be overweight. This is because sufferers don’t usually ‘restrict’ enough between episodes to make up for energy intake during binges. Additionally – purging doesn’t result in removal of most of the energy intake. But what it DOES to is completely screw with your body’s homeostatic mechanisms (both in terms of health and weight /satiety regulation) and the whole process spirals into a vicious cycle.
As touched on above – the alterations in insulin sensitivity and changes in testosterone, cortisol, insulin, DHEA, GH and IGF leads to changes in the distribution of fat mass.
Firstly – there is an alteration in the visceral to subcutaneous fat ratio – with a relative increased in the metabolically active visceral fat (found in the abdomen). This increase in metabolically active fat leads to further abnormality in glucose and triglyceride levels, and compounds / worsens the insulin resistance and cholesterol profile.
Hormonal changes and insulin resistance also lead to an increased propensity to lay down abdominal fat subcutaneously too. This is due to two major hormones – growth hormone and cortisol. Essentially – although normally GH concentration predicts regional body composition (and favors a redistribution of body fat such that Trunk to Extremity fat ratio decreases), in AN the peripheral GH resistance and low IFG-1, in addition to high cortisol, results in a redistribution of mass such that there is a decreased extremity mass and increased central adiposity.
Lastly – There are a number of other alterations that combine to worsen this ‘Mr Potato Head Phenomenon’ – with the abdomen seen as ‘being out of proportion’ to the rest of the body – lean, skinny limbs with a big abdomen. A loss of lean mass (which will cause your limbs to waste away); the fact the abdomen/ torso will always stay ‘larger’ due to bone structure and the housing of organs; Digestive issues as a result of more food being eaten and an increased faecal load; the delay in digestive efficiency – with the intestines needing a few weeks to ‘catch up’ with requirements, and a resultant abdominal discomfort and bloat….
And to finish…
What can you do if you think you are at risk?
Many people with AN or BN cannot easily “reverse” their illness and even after weight gain and normalized eating patterns, many have physiological, behavioral and psychological effects that persist for extended periods of time.
Treatment is challenging and complicated. Why? Frequently, the disorder has been present for some time prior to presentation. There is often denial of the seriousness of the illness, both from patients and family, and often the complexities of the psychological aspects of the disease are lost in the ‘physiological’ recovery. Treatment also requires a coordinated ‘multi-disciplinary approach’ – whether it is done as an outpatient or in a hospital in those cases that are severe or those that have medical complications/ severe malnutrition. Treatment involves: Medical Care in order to help to improve the individual physically and prevent death. Sometimes restoring things such as electrolytes will also help to improve some of the altered behaviors and improve mood; nutritional management which is important to restore weight as well as helping with strategies to deal with anxiety/ concerns surrounding eating/ food; psychological care to help target the root of the issues – with therapy as an individual, or as a family or group, aimed at challenging the abnormal behaviors and ideas; and may require medications (not really all that helpful – however, antidepressants and antipsychotics have been used to varying success and can also help with co morbid depression or anxiety).
So with that – My final word will be this:
If you are experiencing any of these problems, if you think you may have disordered eating, or an eating disorder, the most important thing you can do is go and get help. Although you may THINK you are ‘in control’ – it is very likely you are not. The disease/disorder is. And unless you do something to CHANGE this – Nothing will change.
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References:
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