Leptin Resistance - the permanently hungry horse.

Carol Moreton • Apr 05, 2024

Harnessing Hormones - the science behind leptin resistance.

(Leptin resistance - a condition that complicates weight management by disrupting the horse's natural appetite control mechanisms, leading to overeating and weight gain)

In the complex world of bodily functions, hormones play a pivotal role, orchestrating everything from metabolism to circadian rhythms to mood. These chemical messengers, very often underestimated, have a profound impact on one of our most basic functions: 
appetite.

We’re going to take a look at two of the lesser-known hormones, leptin and ghrelin, and how their critical roles regulate both hunger and fullness, and not just in our horses, but us humans too.

To put some perspective on this, have you ever wondered why, when you break out the box of chocolates, you literally can't stop eating them until the box has gone? Have you ever wondered why you can devour an entire packet of choc-chip cookies, yet you wouldn't do the same for a whole side of wild salmon?


It's not because we're weak-willed or lack self-discipline. It's not that we have no willpower. It's a biological reaction to sugar and carbs, and willpower won't work here.


Personally? I consider myself lucky - I have a savoury palate. Give me Marmite anyday, and no I don't touch sugar - we don't even keep it in the house. If we have visitors and I put the kettle on, suddenly I'm having to apologise profusely for the lack of sugar for their tea or coffee. But if husband brings home a box of Maltesers or Quality Street on a Saturday night, they're gone in one sitting. Shared, of course, but they're gone, and I'm both deliciously happy, courtesy of the massive dopamine reward hormone hit, yet horribly guilty (never mind feeling a bit ick) as it's always completely beyond my control. Sound familiar?


The overweight epidemic – it’s a hormonal perspective

Our modern world presents a paradox where, despite an abundance of food, the majority struggle with being overweight. So what’s driving our eating habits? The answer lies partly with leptin and ghrelin, two hormones that dictate when we feel hungry and when we've had enough. If their respective messages aren’t getting through, or if one is overriding the other, this will affect how appetite is regulated, triggering widespread weight issues.


This has only really been studied since the mid/late 1990s, but is very much an integal part of the IR/EMS horse and Diabetes type II human syndrome. And when it comes to our EMS horses, it's really important for us human carers to understand how and where it fits in.

First up, meet 
ghrelin, the ‘hunger hormone’, which is produced in the stomach, signalling the need to eat. Its levels fluctuate, peaking before meals and lessening after. On the flip side, leptin, the ‘satiety hormone’, signals fullness, which in the perfect world helps to regulate long-term body weight. However, if these signals are compromised, this leads to a perpetual state of hunger or overeating, despite the body's actual needs.


Ghrelin - the drive to eat

Ghrelin's role extends beyond simply signaling hunger; it also stimulates the release of the growth hormone from the pituitary gland, which has wide-ranging effects on energy metabolism and physical growth, i.e. height, bones and muscles. Interestingly, ghrelin levels increase not just before meals but also during periods of calorie restriction, affecting its role in long-term energy balance. Ghrelin's activity is modulated by factors such as sleep, stress, and exercise, making it a target for interventions such as dieting and promoting a healthy weight.


Leptin – the satiety instruction

Leptin, produced by adipose (fat) tissue, acts on receptors in the hypothalamus of the brain, where (sorry – science-y bit coming up …) it inhibits hunger by counteracting the effects of neuropeptide Y (a potent feeding stimulant secreted by the hypothalamus) and by stimulating the synthesis of α-MSH, an appetite suppressant. However, leptin's effectiveness can be weakened by inflammation and a diet’s fatty acid composition. Cue leptin resistance, which is what we see so often in our EMS horses.

It means that less leptin crosses the blood-brain barrier to signal satiety, so the brain thinks the body is still hungry, making our horses think they're still starving, so they continually eat despite adequate or even excessive fat stores.


Obesity - a hormonal mismatch

The discovery of leptin and ghrelin in the 1990s was a breakthrough for science in understanding obesity. It's not simply a matter of willpower; it's a complex interplay of hormones gone wonky. Leptin resistance, for instance, shows how the body ignores the signals of fullness, leading to continuous eating and weight gain. Similarly, elevated ghrelin levels, especially if stressed or sleep-deprived, makes the brain increase cravings for carbohydrates and sugars, i.e. the bad stuff.


Correcting the imbalance of leptin and ghrelin requires more than just dieting or exercising; it needs a functional approach to lifestyle changes. Dump the junk for real food, get adequate sleep, reduce stressors to lower cortisol levels (which when higher trigger more insulin release), and implement a regular exercise routine, even if it’s just walking – all foundational elements. 


Equine insights

Back to our horses, and here’s breaking news – those crests and fat pads aren’t officially made of ‘fat’. Those crests are adipose tissue, formed as a result of the excess insulin/blood glucose, and are almost a separate organ in themselves, created by the endocrine (hormone) system, because the body has now become leptin resistant, a condition that complicates weight management by disrupting the horse's natural appetite control mechanisms, leading to overeating and weight gain.


So, knowing that it’s the adipose (fat) tissue cells which produce the leptin hormone, you’d be forgiven in thinking that our IR cresty equines would produce even more of the leptin’s 'stop eating' instruction to signal the body to eat less food and normalise weight. Well, you'd be right. But because our cresty metabolic/IR/Cushings horses have become leptin resistant, overridden by the brain's demand for carbs, the vital message that they’re no longer hungry isn't being heard. They're only hearing the ghrehlin hormone telling them that they're still hungry and to eat more and more.


As with all hormone issues, leptin resistance is a complex issue and as I type, probably still not fully understood in the horse-world, but there are many factors that can negatively impact leptin levels including (and I quote from esteemed sources) :


  • High fructose, simple carbs and grain consumption.
  • High insulin levels.
  • High stress levels.
  • Overeating.


Kind of obvious I know …


Thing is, we’re up against powerful biochemical mechanisms created by food addiction - willpower becomes useless when sugar is in charge of the brain chemistry. It hijacks the brain, hormones, and metabolism, and the only way to fix this is to rewire the brain. A researcher at the National Institutes of Health (NIH) actually theorises that the real regulator of a body's weight and metabolism isn’t so much the stomach but the brain chemistry - the brain can only hear the carb cravings, so we need to rewire the brain to send the opposite message and shut down that hunger, while working on reducing that crest where the adipose tissue sits. Don't panic - we go into how to do this a little further on ...


Now here's a thing. For those of us who've already been there, we already know how difficult it is to shift that crest! We know our horses are overweight and we need to do something, so thinking we're doing the right thing we restrict their feed/calories, but this doesn’t work and our cresty equines stay cresty. As Juliet Getty (Equine Nutritionist) says:


“The reason is simple . Dieting restricts calories, which lowers the metabolic rate. Weight loss may occur at first, but the body then goes into 'survival mode' and starts to hold on to fat and becomes sluggish in burning calories, making it extremely easy to put all the weight back on.”

Restricting forage is also detrimental, especially for our metabolic equines, because, as we know, the stress involved increases the stress hormone cortisol, which then induces elevated insulin, which as we know promotes the very thing we're trying to reduce - fat storage. And so we’re back where we started.


For the record, Dr Kellon says that all IR horses have leptin resistance, so there we go. Whether we like it or not, we should be factoring leptin resistance into the whole IR/EMS scenario.


Research, implications, and strategies

Recent human studies have shed light on how high-fat diets can lead to alterations in gut microbiota, which in turn impact the production and function of ghrelin and leptin. No surprise, the conclusions suggested a (very obvious) link between diet, gut, and hormonal regulation of appetite.


Furthermore, research into intermittent fasting and time-restricted feeding has revealed significant impacts on the regulation of these two hormones, offering promising avenues for managing appetite and metabolic health. Which of course, we can’t ever do with our horses. But here’s what we can do, and yes, I know it’s all obvious stuff:


  1. Nutritional interventions - research and anecdotal evidence shows that Acetyl L-Carnitine (Alcar) plays a significant role in managing leptin resistance, supporting more effective metabolic regulation.
  2. A species-appropriate fibre-rich diet will improve leptin sensitivity and reduce ghrelin levels, promoting satiety and reducing hunger, so I can’t emphasis enough how important it is to dump those feeds with bulk fillers that trigger gut sensitivities (see our ‘The Feedbowl’ page for the main offenders).
  3. Incorporating anti-inflammatory foods such as omega-3 fatty acids (linseed) can combat inflammation and improve hormonal signalling. 

  4. Lifestyle – I know, I know, but you can’t dispute the science. Regular physical activity, even if it's just walking, is shown to enhance leptin sensitivity and reduce ghrelin levels. Additionally, prioritising rest/sleep and managing stress can help normalise ghrelin and leptin levels.


So let's talk a bit more about Alcar ...


The amino acid Acetyl L-Carnitine (Alcar) - the leptin resistance game changer

When I was swatting all things leptin for Murf (around 2013/14), I came across an interesting article on a forum, written by another horse owner who was also struggling. Quote:


“I read one piece of equine research (a 2004 study by Woolworth et al) ... on the specific subject of l-carnitine and leptin … which indicates that l-carnitine boosts blood concentration of leptin.”


So, more leptin hormone in the bloodstream courtesy of L-Carnitine (Alcar)? So surely a greater chance of the leptin message being heard? The author also wrote that coincidentally she saw Alcar being advertised as a potential human weight loss drug:


“The last time I spoke to a physician about this, albeit not an endocrinologist, I was given to understand that the advertisement isn't entirely spurious, so I assume there is something I'm missing about how leptin resistance works and/or about how l-carnitine works with leptin.”


Very generously, she edited her post 6-months later to say:


“Update … after 6 months of l-carnitine supplementation, leptin blood levels decreased from abnormally high to within normal range. Not a controlled experiment though.”


So to the good news - research and anecdotal evidence shows that Acetyl L-Carnitine (Alcar) plays a significant role in managing leptin resistance. By addressing leptin resistance, we can support more effective metabolic regulation.


Final thoughts - a multifaceted approach to appetite control

The Equine Metabolic Syndrome (EMS) and Insulin Resistance (IR) both highlight how modern management practices have drifted from their natural evolutionary needs, promoting leptin resistance. It’s a given that addressing these issues through diet and lifestyle adjustments is crucial for their well-being.

By understanding the science and addressing the dysregulation of leptin and ghrelin’s place in appetite control, we can look towards improved wellness for our EMS horses. It's perfectly possible to reset their biology rather than fighting against it, by adopting a functional approach that combines dietary changes, lifestyle adjustments, and, where appropriate, targeted interventions to restore hormonal balance.


Personally? I can honestly say, no word of a lie, that getting diet right and feeding Alcar to my metabolics - Murf, Cookie and MacAttack - was a game-changer. It made a profound difference to their original fat-pad, cresty state. Pro-Found. I started feeding it in 2014 and still do to this day. Our TB mare, HRH Queen Carmen, also gets it to help with her musculoskeletal issues (all explained on our Acetyl L Carnitine product page). I swear by it - even take it myself. Product link as per previous sentence, and also in the Shop link below.


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Thing is, these days there's too much histamine going on out there, and it's making many already established health syndromes even worse, with humans and horses alike suffering all the more. Histamine in the right balance is the body’s friend, released when there's an allergic reaction. Simples. We know this. Histamines are a bit like a club's bouncer on the door, helping the body get rid of something that's bothering it, as in an allergy trigger, aka ‘allergen’. Histamines start the process that hustles those allergens out of the body or off the skin. Thing is, there’s a new kid on the block and we need to take notice of it because it’s a now a Big Thing - histamine intolerance. What is it? It's when too much histamine is being made by the body which causes its own allergic response, and the body feels seriously crap. The symptoms can be anything and everything from swelling to fluid retention, and so much more. It’s now recognised as a spectrum illness, with mild, moderate and severe levels to it. So let's dig a little deeper into what histamine is, and why the body is now developing a resistance to it. NB. As is usual, there's very little equine research out there, so this is based on recent human research and comparisons made to our horses. Histamine Histamine itself is found naturally in the body; the body makes it and, yes, we also consume it. It’s released by ‘mast cells’, one of the white blood cell team (the immunity protector cells) and they sit in the body’s connective tissues’ interstitial fluid, which is the thin layer of fluid which surrounds each and every one of the body’s cells. Ideally situated for when they have to spring into action. Mast cells are one of the body’s best friends, having recently been shown to have key roles in the initiation of adaptive immune responses, literally the body's killer army, and specifically relating to their role in allergies . They possess multiple pathogen recognition systems, and store large quantities of fully-active inflammatory mediators, which make them superior immunity sentinels, releasing the very earliest alarm when an offending allergy-triggering offender dares to land on the doorstep. Mast cells contain granules rich in histamine (and also heparin, the blood clot preventer), and release histamine as a first responder to those offending organisms. Yet histamine intolerance is now becoming a new label – it’s become so prevalent these days that there’s even a new medical diagnosis for it – MCAS - Mast Cell Activation Syndrome . MCAS is not just on the rise, it’s significantly on the rise. Most of us are familiar with typical raised histamine conditions/MCAS, i.e. hives, peanut allergy, raised welts from a bee sting, and dermatographia – sounds weird but you may know it - essentially it’s where you scratch your fingernail on your skin and it creates a raised red welt – you can literally write your name on your back in raised letters. Doctors actually use this letter-writing method to determine histamine levels in a patient, because when the mast cells have either excess histamine in them or they release histamine too easily, the body will develop dermatographia, so seeing letters swell up on the skin before your eyes is a surefire way to determine if there are excess levels of histamine in the body. However, there are a whole host of other multiple symptoms now coming to the fore, related to histamine intolerance, but sadly they’re poorly diagnosed, often mistreated, and they're causing real suffering. So, what’s behind this increase in mast cell activation? Here’s one clue for starters, and it’s all to do with our mobile phones and wifi, seriously. A recent Swedish study (Johannsen et al) shows that the effect of EMF - electro magnetic frequencies (mobile phones, mast towers, wifi, you name it) - on mast cells causes susceptible individuals to release more histamine that drives this allergic inflammatory response. Most conventional doctors don’t know about MCAS – their current approach remains that if there’s too much histamine, take an antihistamine. Trouble is, histamine also works as a neurotransmitter – when you take an antihistamine, what happens to you? You get drowsy. Exactly! Because – histamine’s actively involved in the sleep/wake cycle. When histamine’s at high enough levels it stimulates the brain – too much or too little histamine is bad, so when you attempt to block histamine, TaDah! You actually get sleepy. (Science nerd alert - one particular pharma drug out there, Modafinil (sold under the brand name Provigil, among others), is a pharmaceutical medication to treat sleepiness due to narcolepsy, shift work sleep disorder, or obstructive sleep apnea - it actually targets histamine to keep levels higher to keep the brain awake.) What symptoms are now being triggered by MCAS? Food intolerances are common, as many histamine triggers are in the diet, so much so that some people are on restricted diets because certain foods trigger histamine release. Equine-related Clue No.1 . Some foods also contain an amino acid, histadine, mainly found in meat, which when digested is converted into histamine. Normally the body can process this but when there’s too much ingestion of histamine, or too much production of histamine, enter histamine intolerance, typically affecting people with food allergies. So what foods are high in histamine, and best avoided? Bacteria produce histamine, so leftover food, aged cheeses, cured meats - bacteria will start to break down histadine - that's me being careful with last night's leftovers then. I hate to kill the love for fermented foods as well – which for the record also feature highly in our kitchen - but fermented foods are fermented by ... bacteria!. These amazing health foods, sauerkraut, kimchi, miso, yogurt … this is where eating these wonderfully healthful foods, in a person with histamine intolerance, is like putting petrol on a fire. Other symptoms that tend to be misdiagnosed? Allergy brain for starters, feeling fuzzy/foggy in the brain, often with associated bad headaches/migraines, due to excess amounts of histamine which is now known to have an impact on the brain. Then there’s nasal congestion, sinus issues, fatigue, digestive problems, menstrual cycle problems, nausea, vomiting … and if it’s really severe we’re into cramping, palpitations, anxiety, wonky temperature regulation. Then there’s oedema, fluid retention, swelling, puffy legs – sound familiar? Cue equine-related Clue No.2. Why? Because histamine has a direct action on the lymphatic system . Those mast cells, filled with too much histamine, sitting in the interstitial fluid surrounding every cell in the body, are now leaking the excess histamine straight into the lymph fluid, which, when it’s overburdened with toxins and twinned with lack of movement, becomes sluggish and the flow slows down, resulting in swelling/oedema. Another connection – and yes it relates to my favourite topics – leaky gut and the microbiome - cue equine-relatied Clue No. 3. When the body has dysbiosis of the microbiome (SIBO - small intestinal bacterial overload) , the negative gut microbes (bacteria again!) cause the mast cells to produce more histamine. When there’s excess histamine in the digestive tract, enter food intolerances. Equally, the negative bacteria may be causing the digestive breakdown of histadine into histamine, so it’s that old dodgy-gut thing again. Diagnosis So how does a doctor diagnose these various symptoms as a histamine intolerance? What tests - other than a SIBO test - are there? Well, as per usual, testing hasn’t reached our horse world, so we can only go by the human world. Currently, histamine can be measured in the blood; another marker for mast cell activation, the enzyme tryptase, can also be measured; also n-methyl histamine, a breakdown product of histamine, can be measured. There are many more methods, i.e. enzyme testing and so on, but if I ran through them all here your eyes would glaze over. Ultimately it all comes down to one size does not fit all . We’re all unique, whether horse or human, and it’s all about precision food medicine, as in precision nutrition. Some people do great on vegan diets; others do terribly. Some do brilliantly on Keto, others not so. Eating avocados and shellfish might be great for some, but might be killing others, never mind the wine and beer we (I) love so much as well! And as for our horses, some aren't bothered at all by the spring pollens - others are floored by it. It’s very much about personalising what’s right for that particulary genetic make-up – every individual body is different. To quote one of my favourite Function Medicine doctors, "Genes load the gun, but it's diet, lifestyle, and environment exposures that pull the trigger." Where does Functional Medicine fit in? Which links us nicely to one of the many concepts of Functional Medicine , where one disease (as in dis-ease, where the body is ill at ease) can have many causes - histamine intolerance is not alone here as it can have many causes. And one cause, such as that great masquerader, Lyme disease , can create many diseases across the board, such as neurological issues, joint and skin issues, chronic fatigue, dementia ... the list goes on. And … lyme is also associated with histamine intolerance because the lyme bacteria resides/hides in the connective tissue in the body, which in turn can activate the mast cells. There are also a lot of drugs that can interfere with histamine and warning, this list is scary – antibiotics, antidepressants, antipsychotics, diuretics; even muscle relaxants, pain meds, my nemesis PPIs ... even over the counter meds like Aspirin – all can be driving this histamine intolerance. Cue equine-related Clue No 4 - several meds here relating to horses ☹ It’s been shown that certain nutrients can break down histamine, i.e the B-vits 1, 6 and 12, folate, vit.C, copper, zinc, magnesium, calcium - all critical nutrients, and foods high in Quercetin, a natural antihistamine. Ginkgo biloba is high in quercetin (also said to be beneficial for Covid), as is good old Turmeric . As is my friend, the odd glass of red wine 😉 The wondrous and super-nutritious Nettle is also known as a beneficial antihistamine as it can block the receptor sites that histamine usually latches on to, all due to its antagonist/negative agonist activity but I won't blind you with the science behind that one. And remember the enzyme tryptase from earlier, that's released alongside histamine and which promotes its effects? Nettle also inhibits tryptase - clever nettle. Both Ginkgo and Nettle feature in our PollenTonic blend. Which links us nicely to our horses Definite clues and comparisons to be had here – certainly the lymphatic connection, i.e. puffy leg syndrome, lymphangitis, CPL (chronic progressive lymphodema). And of course, all those spring tree pollens and summer grass pollens are all dumping themselves on our horses’ grazing, with no doubt plenty of pollen residue in their hay as well, which they’re then ingesting. When you look at the Big Picture, ultimately it’s yet another case of removing the bad, replacing with the right food and nutrients, looking after the microbiome, fixing the leaky gut, and letting the healing begin. Originally written Jul'21, copied over from our old website
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