Gabor Szendi:
What can we do after a brain injury? Or rather before it

Medicine is fairly powerless regarding brain injuries and their prevention. If disease occurs, Doctors try to keep the patient alive, and wait for nature to heal the injuries. But Doctors could do much more, if they believed in the extraordinary effects of vitamins.

 

 

It sounds rather surprising, but the summary about acute brain injuries written by a research team at Cambridge University in England starts this way: 'To date, there is no specific drug treatment for acute brain injury...' (Carpenter et al., 2015). Naturally, this does not mean that medicine has no tools at all; in fact a lot can be done to prevent further damage, and during and after convalescence many drugs are used to decrease different functional impairments (Zasler et al.; 2006). And of course physiotherapy plays an important role in rehabilitation. It may seem that this is where science stands, and in this field, 'The physician treats, but nature heals' seems especially true. But how does nature heal?

Can we stimulate nature somehow?

The main goal of the treatment of patients after brain injury or stroke is to reduce the development of secondary damage due to the injury. Research conducted in the Bronx-Lebanon Hospital of New York came up with the surprising result that among patients admitted to the intensive care unit, the ones with severe vitamin D insufficiency (lower than 20ng/ml blood level) were 8.7 times more likely to die than those with the same condition, but normal vitamin-D levels (Venkatran et al., 2011).

In patients admitted to hospital in the Italian city of Perugia the extent of brain injury and the neurological deficit of the patient was higher if the patient had a lower vitamin C level (Polidor et al., 2001). And in the Turkish Selçuk University hospital the severity of stroke patients' condition correlated with the degree of vitamin B9 (folate) and B12 deficiency (Bayir et al., 2010).

Who has ever heard of such thing: that patients are treated with vitamins after brain injury?

Dr. Ray Matthews, the leader of the Surgical Intensive Care Unit of Grady Hospital in Atlanta, and a recognized vitamin-D researcher on the margins, became a 'magazine hero', when a 17-year old girl who suffered a severe car accident recovered totally using his protocol. From such a severe similar brain injury 50% of patients die, and 47% fall into a coma for good. Instead, as soon as she was admitted to the hospital, the girl received vitamin-D, omega-3, glutamine and progesterone infusions (Finkel, 2013).

It seems the healing power of 'nature' is only too material, however modern medicine does not take note of it in everyday practice.

What does the brain need for healing?

It is natural that for the regeneration of brain tissue special substances are needed, furthermore it increases the chance of healing if the toxic materials from necrotic, decomposing tissues are neutralized by proper antidotes, and the inflammatory and excitation processes caused by the injury are deactivated. The Western diet on which the injured patient feeds before hospital admission is poor in these nutrient-protective substances, and unfortunately the hospital continues to provide the same or an even worse diet.

B vitamins

According to the research cited earlier, the blood levels of vitamin B9 and B12 were prognostic regarding the extent of brain injury and the risk of death. Concerning significant healing effects of vitamin B3 (nicotinamide) and B6 there is currently only promising animal test data available. Although they act together, research has neglected the role of other B vitamins, and in developed countries significant deficiencies of certain types of B vitamins are present (Kennedy, 2016). Since, if the recommended dosages are not exceeded, giving B vitamins is harmless, the results of animal research could have been transferred into clinical practice too. It is important to note that half of Hungarians insufficiently utilize folic acid, the synthetic version of folate, therefore it is well worth giving patients active folate (Szendi, 2018). Folate and vitamin B12 play important roles in DNA reading, which plays a crucial role in brain regeneration.

Choline

Choline used to be known as vitamin B4. It plays a vital role in the development and working of the brain, and in brain regeneration after injury, because it is essential in the synthesis of phospholipids, which make up cell walls, and dopamine and acetylcholine, which are neurotransmitters. Choline deficiency is common, and half of people would need increased intake due for genetic reasons. Citicoline, which was developed in Japan for stroke treatment, has a higher therapeutic effect. Studies are controversial, some found that with the use of Citicoline (1000-2000 mg daily) healing is faster and more complete (IOM, 2011), and it improves memory and the ability to think significantly in neurodegenerative diseases (Gareri et al., 2015). In a review, Citicoline was found to be safe and effective in the treatment of stroke patients (Overgaard, 2014).

Vitamin D

70-80% of Hungarians suffer from severe vitamin D insufficiency. Vitamin D is necessary not only in bone building. In fact, it is a hormone that has a different function in every tissue of the body. Each neuron and glial cell in the brain contains vitamin D receptors. Vitamin D protects neurons, decreases inflammation and oxidative injury in the brain, enhances NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) production (Molendijk et al., 2012; Eyles et at., 2011).

In follow-up studies over years, people with the lowest vitamin D levels had 1.5-2.5 times higher risk of stroke compared to people with higher levels (Sun et al., 2012) and in the case of stroke, the extent of brain damage is 10 times higher (Li et al., 2017). People with normal vitamin D levels have twice the chance of successful recovery from stoke (Park et al., 2015). In a study conducted in Peking, 220 post-stroke patients were followed up. Patients with the highest vitamin D levels had one tenth of the chance of recurrent stroke and death, than patients with the lowest vitamin D levels (Qiu et al., 2017).

In an Indian study, vitamin D deficient patients were divided into two groups. On admission one group received a 600,000 IU vitamin D injection besides the conventional treatment. Three months later the improvement in the vitamin D injection group was 3 times higher (Narasimhan et Balasubramanian, 2017).

Vitamin C and E

The antioxidant role of Vitamins C and E provides the reason to discuss these two vitamins together. Oxidant effects cause severe secondary damage in brain injury. Compared to other tissues the vitamin C concentration is 100 times higher in the brain, and it decreases significantly in brain injury (IOM, 2011). As cited earlier, the extent of tissue and functional damage in stroke correlates with the decrease of vitamin C level (Polidori et al., 2001).

The 10-year follow up of more than 20,000 people demonstrated that those with the highest vitamin C levels had a 42% lower chance of stroke compared to those with the lowest levels (Myint et al., 2008), and low vitamin C levels may cause spontaneous hemorrhagic stroke (Vannier et al., 2014).

It has been long known that after severe injuries the vitamin C need of the body increases extremely and intensive supplementation is needed (Long et al., 2003). In a placebo control study, high dose vitamin C infusion (10 grams on the first day, then 4 grams daily) reduced the extent of brain injury, and the co-administration of 400 mg of vitamin E daily reduced mortality (Razmkon et al., 2011).

Omega-3: an important element for the brain

The consumption of sea creatures containing omega-3 was a crucial factor in the evolution of the human brain. 50-60% of the dry-matter content of the brain is fat, and a significant amount of it is DHA (docosahexaenoic acid), a type of omega-3 fatty acid (Weiser et al., 2016). Omega-3 is not only an important building material, but also a strong anti-inflammatory agent, neutralizing the harmful effects of free radicals, and reducing BDNF production (We et al., 2004). Several case-studies have been published, showing that omega-3 helped injured people recover from very serious, comatic conditions (Lewis, 2016).

The most effective antioxidant: uric acid

Compared to other mammals, the level of uric acid in humans, even in normal cases, is outstandingly high. The reason for this is that when we lost our capacity to synthetize vitamin C, uric acid became the strongest antioxidant in the body, and to provide high blood levels, many genes that were responsible for the excretion of uric acid became inactivated.

Western medicine sees high uric acid levels as a problem, although it has a pronounced advantage in brain injuries and neurodegenerative diseases. The reason for the inconsistency is that high uric acid levels can be constitutional characteristics, but can also be elevated due to pathological reasons such as metabolic syndrome, and kidney failure (Szendi, 2015).

In stroke patients each 1mg/dl elevation of the uric acid level increased the chance of good recovery by 12% (Chamorro et al., 2002). In another study, women after stroke who received 1g/day uric acid infusions had double the chance of recovery compared to the placebo group (Llull et al., 2015). Many studies have found the use of inosine that increases the level of uric acid to be safe and effective as well, for example it also enhances the growth of axons (Benowitz et Carmichael, 2010).

Cholesterol: is it good to lower it?

The literature of cholesterol lowering medications is unusually contaminated with reports from the pharmaceutical industry that highlight the positive effects, therefore it is extremely difficult to take a correct standpoint on this question. The weight of the brain is1-2% of bodyweight, yet it contains 23% of the cholesterol in the body. The brain is cholesterol self-sufficient, and cholesterol from the blood cannot cross the blood-brain barrier, therefore studies that demonstrate a correlation between blood cholesterol and brain diseases lack credibility (Martín et al., 2014).

Half of the brain's dry-matter content is cholesterol which proves the eminent role of cholesterol in different brain cells (Wainwright et al., 2009). Some cholesterol lowering medications can cross the blood-brain barrier so they can decrease the cholesterol levels of the brain. This usually has a negative effect on brain function (Golomb and Evans, 2008), therefore it is difficult to believe in studies that show an advantage in convalescence and/or survival in patients taking statins, compared to patients not taking them before or after brain injury. Many studies have disproved the protective effect of statins (Orlando et al., 2017), and more than one study found the taking of these drugs to be expressly harmful (Scheitz et al., 2014). In several studies cholesterol lowering drugs increased the risk of hemorrhagic stroke, and in one study the risk increased by 66% (Wainwright et al., 2009). Therefore the practice of treating stroke patients with cholesterol lowering drugs is strongly arguable.

Brain plasticity

For a long time it has been unimaginable that brain tissue can regenerate from its injuries, in a similar manner as broken bones join, and wounds heal. It was presumed that new neurons and new neural pathways cannot develop, and even if certain patients with brain injuries had some improvement that still did not change the way of thinking about the brain. As a medical student in 1969, Paul Bach-y-Rita faced his poet and philosopher father's severe stroke that led to aphasia and total hemiparesis. Bach-y-Rita started on a seemingly impossible task: he felt he had nothing to lose, so he taught his father how to move on all fours. After several months of intensive practice, miraculously, his father was able to move his paralyzed body parts again. Then he stood up, learned to type, learned to talk again and once, surprising everybody he sat on a chair again and continued his life as if he had simply come back from a long journey. His recovery led to the conclusion that his stroke was not as severe as was first thought. But when seven years later Bach-y-Rita's father died of a heart attack during mountain climbing (!) the autopsy showed that half of his brain was atrophied (Doidge, 2007). That is how Bach-y-Rita became a researcher into brain plasticity.

Brain imaging methods have meant a breakthrough in theoretical research, because they make visible how the brain rearranges itself after an injury. Now we know that the recovery of the father, Pedro Bach-y-Rita was not an exceptional miracle, but the result of the work of healing mechanisms developed during evolution.

Unfortunately, the therapeutic use of this recognition still lags behind. Nowadays rehabilitation aims to replace the missing functions in working limbs. But the 'miracle' recipe exists already, it is called constraint-induced movement therapy. The Behavioral Neuroscientist Edward Taub, who developed the method, conducted experiments during the 1970s in which he induced paralysis in one of the limbs of monkeys, and then restricted the movement of the intact limb, rewarding the use of the injured one. Monkeys were soon able to move their injured limb properly again. Later Taub tried his method on post-stroke patients. There was one patient whose hand had been paralyzed for 18 years. The healthy limb was restricted for a whole day at a time, and the patient's task was to try to use the paralyzed limb in various activities. Spectacular improvements could be noticed in just a few weeks (Taub et al., 1994). The method is used successfully today to restore many other missing functions due to neurological diseases. It can be confirmed with brain imaging techniques that parallel the improvements, and continuous neuronal rearrangement can be noted in the brain (Könönen et al., 2012).

It is not by chance however, that even though the method is successful, it is not used in therapeutic practice, because the relearning of missing functions is a heroic task for both the patient and physiotherapist.

 

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