Alcohol intolerance in CFS - gives us a clue as to the mechanisms of fatigue

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[UPDATED MARCH 2022]

Introduction

Alcohol intolerance is extremely common, if not universal, in patients with CFS/ME. Indeed during the 1980s, I chatted away with Professor Fields at Warwick University, who was diagnosing ME at that time, and he would not diagnose ME unless there was alcohol intolerance! I suspect there are many possible mechanisms for alcohol intolerance and these are symptomatic of other problems that also result in fatigue.

Upper fermenting gut

[See Fermentation in the gut and CFS and Fermenting gut - the Full Monty]
The fermenting gut produces a large toxic load to the liver. Products of fermentation could include ethyl alcohol, propyl alcohol, butyl alcohol, D-lactate, hydrogen sulphide and probably other toxins. All the blood from the gut passes via the portal vein directly to the liver. The liver is responsible for preventing these toxins spilling over into the bloodstream and circulating systemically. This is important both because these toxins can inhibit mitochondrial function (and give us the symptom of fatigue), and also because these toxins can interfere with brain chemistry resulting in the symptoms of foggy brain and mood changes. The symptoms of fatigue and foggy brain are cardinal in CFS/ME and mood changes are extremely common.

We know that it is extremely hard metabolic work for the liver to maintain homeostasis in the body. (Homeostasis – (from Greek: “hómoios” – “similar” and “stásis”, “standing still”), is the property of a system in which variables are regulated so that internal conditions remain stable and relatively constant.) Maintaining homeostasis by the liver is greatly demanding of micronutrients such as B vitamins, minerals and essential fatty acids (we know this because liver is an extremely nutritious food to eat!). It is also greatly demanding of energy – indeed at rest the liver consumes 27% of the total energy generated in the body – this is more energy than the heart and brain combined!

Alcohol, when drunk, is consumed in gram amounts over seconds – that is at least ten and possibly one hundred-fold higher than the rate at which toxins are produced in the gut. So, there is the strong likelihood of the liver being unable to cope as it is receiving toxins (from the alcohol) at a rate far higher than it is used to being able to deal with them (from the gut). In healthy people the liver has a large metabolic capacity and can usually deal with this pretty well. Having said that, (and this is the desired effect when drinking!),sometimes even the liver is overwhelmed and most of the alcohol spills over into the bloodstream and gives us that feeling of being relaxed, dizzy and delightful. So CFS/ME patients would suffer adversely from the effects of alcohol, over and above the extent to which healthy individuals do, for two reasons; firstly alcohol will be incompletely metabolised in the liver and secondly alcohol impacts directly on the brain – see below. Regarding the metabolism of alcohol, there are two stages to this:

  • firstly,oxidation to acetaldehyde (which is extremely toxic and gives us hangover symptoms) and
  • a second stage to acetic acid or vinegar which is innocuous and easily excreted.

The incomplete metabolism of alcohol in CFS/ME sufferers is caused both by the fact that the CFS/ME sufferer will have poor mitochondrial status and so will not have the ready supply of the high demands of energy required for these metabolic tasks and also by the fact there may be nutritional deficiencies present in the CFS/ME sufferer that will further limit her liver’s ability to metabolise. These deficiencies are often precisely in those micronutrients required for good liver function, namely, B vitamins, minerals in general and essential fatty acids. The direct impact of alcohol on the brain is now considered.

The effect of alcohol on the brain

The brain is also greatly demanding of energy – at rest it consumes about 20% of the body’s total energy production. Energy production in the brain cannot be explained by mitochondrial function – there simply aren’t enough mitochondria to do such. The brain is largely composed of fat contained within the myelin sheaths – these are Swiss rolls of membranes which wrap round nerves and this myelin sheath has adopted mitochondrial biochemistry to deliver energy. The business of conducting a nerve impulse requires large amounts of energy and this is provided locally in the myelin sheath – this is a very efficient mechanism with energy being produced and used in close proximity. The efficiency results directly from this proximity – producing energy where it is physically needed means that (far) less of the energy produced is ‘wasted’ in ‘transporting’ the energy to where it is needed than would otherwise be the case. It is like having the power station right next to the factory! The myelin sheath membranes have to be of just the right consistency to hold the enzymes responsible for making energy in the right three-dimensional configuration to allow for efficient energy delivery. The problem with alcohol is that it slightly “dissolves” these membranes, probably making them a little bit more liquid than they should be, and therefore distorting the three dimensional configuration. This disrupts the efficient business of energy delivery and it is this impairment of energy delivery that causes the symptoms of foggy brain, poor memory and the ‘guess what, I couldn’t care less’ sensation of alcohol. Indeed this is the mechanism of general anaesthetics – the more fat soluble the general anaesthetic the lower the dose necessary to get an effect – alcohol is very fat soluble and so relatively low doses are ‘’needed’’ for an anaesthetic effect.

Please see Theories of general anaesthetic action As avid viewers of 'Westerns' will know, where John Wayne can often be seen swigging whiskey before having a bullet removed from his arm or an arrow from his chest, alcohol can indeed be used as a general (or indeed local) anaesthetic!

It is possible that this 'dissolving effect', which the alcohol causes in the myelin sheath membranes, is more marked in CFS/ME sufferers, thereby increasing this effect for the CFS/ME cohort as compared with the 'normal' background population.

So, in addition, and as noted above, alcohol impairs energy delivery to the brain. Also see Brain fog - poor memory, difficulty thinking clearly etc

Allergy

Alcohol is made by the fermentation of substrate. This is carried out by yeast and so all alcoholic drinks will contain traces of yeast antigen, together with the substrate from which it was fermented. Beer therefore will contain barley antigen (possibly gluten), wine will contain grape antigen and so on. So some people will react to alcohol for reasons of allergy, for example gluten allergy. If this is the case then generally speaking the spirits are better tolerated than the wines and beers because the alcohol has been distilled off, removing most of the antigen. Once again, this effect will often be more marked in the CFS/ME cohort than in the general background population because allergy is a very common feature in CFS/ME.

Hypoglycaemia

Alcohol also has a direct effect on blood sugar levels-- it tends to drop blood sugar levels. Indeed this is why a glass of alcohol before a meal is often welcomed because it stimulates the appetite. However many alcohols are consumed with sweet additives, such as sweet wine or beer, and this has the opposite effect by spiking blood sugar levels. Alcohol is also addictive – you can always tell the addicts because they drink quickly on an empty stomach – this means that levels of alcohol in the blood rise very quickly and it is the rate at which levels rise that determine the addictive hit! This is very similar to heroin addicts – they are not content with chewing the stuff but inject it intravenously. The problem with the addictive hit is that it stimulates a hormonal response which may be

-- insulin if blood sugars rise quickly

Or

-- adrenalin if blood sugars fall quickly

and this further dysregulates blood sugar levels and energy delivery mechanisms.

So, hypoglycaemia results from the changes in blood sugar levels as a result of the natural tendency of alcohol to drop sugar levels and also perhaps because of the sweet additives in some alcohols, which will tend to spike sugar levels, and finally there is the ‘’addict’’ hormonal effect described above. Hypoglycaemia therefore naturally disrupts energy delivery mechanisms and this will impact disproportionately on the CFS/ME sufferer who is already suffering with energy delivery dysfunction. Please see Hypoglycaemia - the full story

Micronutrient deficiencies

Alcohol drinking itself induces micronutrient deficiencies (I remember John McLaren Howard telling me that anybody who drinks any amount of alcohol and is not taking a supplement will be thiamine deficient). In addition alcohol requires energy for its detoxification – if energy delivery is poor, as it will be in CFS/ME patients, then that will tip the energy balance even further in the wrong direction, as energy will be required for alcohol detoxification.

So, CFS/ME patients, in particular, face a vicious cycle here – they probably already have, for example, micronutrient deficiencies (or at best are supplementing to correct these deficiencies) and then if they consume alcohol, this will worsen these deficiencies, but we have already seen that these micronutrient deficiencies lessen the ability of the liver to metabolise properly, further worsening the effect of alcohol consumption to the CFS/ME sufferer! Coupled with all this, the CFS/ME sufferer has poorer energy delivery mechanisms and so the effect of the above vicious cycle will be heightened by her inability to detoxify alcohol as well as a healthy person!

It is also the case that the combination of all of the above effects will create lots of other vicious cycles for the CFS/ME sufferer.

Conclusion

So alcohol intolerance, and the nature of it, and the symptoms experienced by the individual concerned help to give us clues as to the mechanisms that are causing symptoms in that individual.

For example, if a sufferer reacts more to wines and beers than to vodka or brandy then that sufferer is more likely to have a significant element of allergy in their response mechanism to alcohol and therefore allergy may well be a significant factor in the mechanism that is causing fatigue in that individual.

Recovery from CFS/ME is often accompanied by alcohol tolerance. Phew! What a relief! Perhaps we should be using this as a test?

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