By Meleni Aldridge
Executive Coordinator, ANH-Intl

Human physiology has developed robust reactions that aim to ensure survival of the species. But these robust reactions are not always beneficial to the body, producing diseases and disease consequences as a result. From the perspective of evolutionary medicine, it is becoming increasingly apparent that Alzheimer's disease (AD) is one such robust reaction — a non-permissive brain disorder, or human hibernation reaction, as a last ditch strategy to survive and protect against potentially fatal immunological and metabolic danger. Owing to their fundamental nature, the metabolic and immune systems were among the first systems to evolve in living creatures. This has made them somewhat symbiotic and inseparable when responding to challenge. Successful approaches to treating the cause of disease must therefore address potential imbalances in both. 

Partial pieces of the Alzheimer's puzzle?

It's 2013 and if nothing else, we can be sure of three things. Firstly, chronic inflammatory diseases (CID) are rising in frequency, but successful treatment is still in its infancy. Secondly, many of the chronic diseases that plague the modern industrialised world never existed 200 years ago, albeit we live on average somewhat longer. And, thirdly, despite the obscene sums of money changing hands in healthcare, conventional medicine is doing precious little to address the real origins of these diseases. Evolutionary selection pressure has shaped human physiology to survive and reproduce, promoting direct survival over reproduction. Yet very few heads seem to be turned towards evolutionary medicine as a means to understand CID and the systemic consequences of a chronically activated immune system.

A new study, being hailed by many as a major breakthrough in the treatment of AD, centres on B vitamins. Participants took 20 mg B6, 500 mcg B12 and 800 mcg folic acid, then 168 out of the total 271 received brain scans. There's no denying that the results were hugely significant. Those taking the B vitamins had around half the amount of brain shrinkage associated with AD as against those taking the placebo. But is this really the whole story?

Well-known UK nutritional practitioner and author, Patrick Holford says, triumphantly, "The bottom line is that we can prevent half of all cases of Alzheimer's disease, saving billions, based on the evidence to date. This shows that, in those with blood homocysteine levels above 10 μmol/L (that's almost half of all people above 60) giving high dose B vitamins (B6 20mg, B12 500mcg, folic acid 800mcg) effectively stops both the accelerated brain shrinkage and memory loss, which are the two hallmarks of Alzheimer's. In an enlightened world we would screen for cognitive function from age 50, test for homocysteine if results not great, then prescribe B vitamins. That's why we set up the free on-line Cognitive Function test at" He goes on to say, "It is extraordinary to think that, not only is all this evidence being ignored and side-lined, but EU laws actually threaten to outlaw the very supplements that we would need to prevent Alzheimer's." 

But are these essential vitamins treating the symptoms or the cause?

Whilst B vitamins are hugely important for energy metabolism and keeping homocysteine levels in check, are they really the solution to preventing AD rather than managing its symptoms? Looking through an evolutionary medicine lens, the answer is probably no. The experience of the participant who spoke of his supplement holiday only to suffer a return of his symptoms would attest to their amelioration effect certainly, but B vitamins alone are clearly not addressing the cause. It's also important to note that only those with high homocysteine levels (over 13 μmol/L, normal parameters being around 7-10 μmol/L) benefited from taking such doses of B vitamins, and the study failed to answer the important question about whether brain shrinkage actually causes you to lose your memory.

Disposable organs

Our regulatory mechanisms (neuroendocrine and immune systems) evolved to cope with short life-threatening challenges such as sepsis or wound healing, and short non-life-threatening episodes. But not to deal with the persistent chronic activation we see today.  The use of old survival mechanisms to deal with modern challenges results in CID symptoms that are 'borrowed' from the way we have always dealt with inflammatory challenges throughout our evolution. This means simply that our survival reaction to financial and emotional stress, sickness and obesity, for instance, is the same now as it was when we were running from or fighting off a sabre-toothed tiger. It's just that when we survived the tiger, it was over, and the immune and neuroendocrine systems stood down allowing normal homeostasis to return. 

In today's world, the stress is persistent, leading to chronic activation of the immune system, which diverts a huge amount of resources to assuage the heavy energy demand.  In some clinical circles, this has earned it the term, 'the selfish immune system'. Having moved from normal homeostasis where the 'selfish brain' is 'king' with first dibs on energy resources, the selfish immune system now takes over. Organs and tissues not involved in direct survival are downgraded to only the most basic of functions and all available energy is diverted to the energy-expensive immune system. Creating what we recognise as sickness behaviour. This is all perfectly normal and healthy when it occurs for a very short period of time, but extended over weeks, months or years, creates a situation where organs are 'disposed' of in an attempt to protect against multiple organ failure as there just isn’t enough energy to go round.

Biological priorities and the brain 

Brain function, blood circulation and anatomy are disturbed in patients with CID, such as AD, Parkinson's disease, fibromyalgia, depression and chronic fatigue syndrome. Whilst it's always been thought that the brain remains 'king' no matter which other organs are disposed of, these symptoms point to the selfish brain being deposed and overridden by another system — the hugely energy expensive immune system.

During evolution, long-term involvement of the central nervous system in stressful situations has been rare and it may be that the occurrence of these brain diseases can only be explained by the presence of danger signals that remain unsolved or register as unsolvable. So whilst no one would ever choose to develop AD or any other brain disease, from an evolutionary perspective, it may be the involuntary choice to ensure survival. A robust reaction to cope with a low metabolic energetic state arising from chronic inflammation and persistent activation of the immune system rather than dying from multiple organ failure. 

Inflammation is lifesaving when controlled and lasting for a short duration, but deadly when not. Danger appears to put the immune system on top in hierarchy, which overrides the 'selfish brain'. Persistent inflammation is considered dangerous to survival, and persistent inflammation that lasts over years, even decades, may be registered as an unsolvable danger. Energy conflicts and danger share the same phenomena during evolution. Therefore, exposure to chronic or multiple dangers should be considered the universal way of developing disease.    

Energy conflicts leading to metabolic hibernation

The longer inflammation lasts the more organs and substances are co-opted by the immune system. Chronic stress and low-grade inflammation can become immune suppressive, which in itself can be protective to prevent further damage. It's been found that AD patients show a higher body temperature but low brain metabolism and temperature, as you would expect when the body is inflamed, but the brain 'disposed' of. On the contrary, healthy older people demonstrate lower body temperature and energy saving strategies like slightly lower metabolism, but normal brain function. The same strategy used in all mammals and humans during calorie restriction.

Whilst humans can't truly hibernate in the strict sense of the word, a number of parallels can be drawn. During the reduced physiological activity of torpor, animals show Alzheimer-anatomy. But unlike humans, these changes disappear 72 hours after emerging. Persistent low-grade inflammation can produce a metabolically-induced hibernation through reduced activity of the thyroid gland in order to conserve energy to divert to the immune system. Is it possible then that AD develops because of an evolutionary conserved mammalian hibernation response that causes a low brain metabolic rate in order to put the immune system at rest? In this way, the pathways leading to AD, whilst pathological, are actually protective

Internationally acclaimed clinical psychoneuroimmunologist, Leo Pruimboom, concurs saying, "Several genes and their proteins associated with increased Alzheimer's disease susceptibility, also have pro-inflammatory functions providing protection against infection". He elucidates further, saying, "The high number of pathogenic microbes in the brain of Alzheimer’s disease patients can only be explained when individuals have been challenged by these microbes during decades, perhaps because of increased permeability of the gut and the mouth barrier as evidenced by the presence of antibodies against oral bacteria in patients suffering from Alzheimer’s disease.  It is conceivable that the person suffering from Alzheimer’s disease reached the age of clinical symptomatology because of his/her highly effective pro-inflammatory functioning immune system. This activity protects the person against infection but at the price of slow neurodegeneration".

Downstream prevention, upstream effects

The real causes of AD, like so many other diseases, are decades downstream from the evidence of the first symptoms. Yet there is still no real attempt at preventative healthcare or education about the hugely deleterious effects of persistent, chronic, low-grade inflammation. If evolutionary medicine is on the right track with regards AD, then the answers surely lie in the symbiotic and inseparable relationship of the immune and metabolic systems rather than throwing good money after bad in expensive upstream drug trials? 

With the evidence from the B vitamin study offering promising support for AD patients, medical journalist, Jerome Burne, draws our attention to the unpalatable reality of modern healthcare. Despite the proof that cheap-as-chips, no side-effects, B vitamins can slow down brain shrinkage, a £2 million drug trial on blood pressure drug Losartan is due to start later this year to explore exactly the same effects! 

As conventional medical science seems to descend ever further into pantomime, maybe it's time we all shouted in unison, "it's behind you"! This time it really is – way downstream.