Serotonin and Neurological Afflictions

Hi,

Last week we saw how eating a tryptophan-rich diet didn’ t necessarily translate into increased serotonin levels in the brain unless backed by adequate Vitamin B3, B6 and complex carbohydrates. It however, did place one a better chance at getting a serotonin boost.

Studies have established some links to a defecient state of brain serotonin with other neurological afflictions besides migraines, such as alcoholism, depression, suicidal tendencies, PTSD, obsessive compulsive disorders, generalised anxiety disorders and social phobia to name a few.

We may experience low brain serotonin levels due to a variety of reasons:

1. Low levels of production of brain serotonin.

2. Less number of serotonin receptors in our brain region

3. High reuptake rate of serotonin back from the synapse into the presynaptic neurons, and

4. Defeciency in tryptophan levels in our body.

There is a new and fifth interesting dimension that has cropped up – that of the serotonin transporter gene (SERT). To relay a message, a neuron releases serotonin into the synapse or the gap between two neurons from where their dendrites begin. Once the message is relayed to the next neuron, the released serotonin in the synapse is collected and transported back to the pre-synaptic neuron by the SERT. SERTS are monoamine proteins. It has been found that when there are changes in the SERT metabolism, neurological afflictions begin.

It is also now being thought that the gene (called SLC6A4 – Solute Carrier family 6, member 4) that encodes the SERT can be mutated and result in changing the functions of SERT.

The area (aka promotor) in the gene SLC6A4 which synthesises RNA under the instrucions from DNA, contains polymorphism – some long repeats (16 repeats of a sequence) and some short repeats (14 repeats of a sequence). Shorter repeats obviously enable lesser coding in them and thus when we have a pair of short repeats we get an increase in the risks of developing disorder states.

So though SSRIs and beta blockers may help migraineurs as well as those suffering from insomnia, depression, PTSD and other anxiety disorders, their efficacy will not be the same between 2 persons with the same condition. Those predisposed to neurological and psychological conditions due to the presence of 2 short versions of the gene will be less benefitted than those with other variations (2 long or 1 long and 1 short).

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Why eating tryptophan-rich foods may not increase brain serotonin

Hi,

I will continue on the note of last week.  Tryptophan, as I said earlier, is one of the 14 essential amino acids (building blocks of proteins) we need to get through food. (Examples of  other essential amino acids are Tyrosine, Phenylanine, Valine, Leucine, Isoleucine, Taurine, Glutamine, Alanine and Asparagnine etc)  

Tryptophan is especially essential for migraineurs as they form the raw material for serotonin – the key player in migraine occurence and prevention. Unlike most of the other essential amino acids, tryptophan has large molecular structure (as shown in my last post). Such large molecules are not allowed through the blood-brain barrier.  

We must understand that tryptophan is required in only trace quantities by the body. The RDA value for it is set at 0.2 grams. Our meals on an average provide us anything between 1 to 1.5 grams every day. Yet only a small fraction of it reaches our brain where it is needed most. Let us see how the scarce tryptophan can play truant in the various stages of it’s metabolisation:

Stage #1: Tryptophan is first broken down by the enzyme Tryptophan Hydroxylase with the help of Vitamin B3 (or Niacinamide) into 5HTP. Here is Catch #1: It might so happen that you are deficient in Vitamin B3, which will spin into action a whole new string of events in the body. When the liver encounters the dietary tryptophan in the absence of adequate levels of Vitamin B3, it will use the scarce tryptophan to manufacture Vitamin B3. It does so at a very steep ratio of  60mg of tryptophan to produce 1mg of Vitamin B3!!

Stage # 2: Here, another enzyme called Decarboxylase converts 5HTP to 5HT with the help of Vitamin B6. Catch # 2: In the liver, tryptophan is metabolised using the enzyme tryptophan pyrrolase. However, if you are even mildly deficient in Vitamin B6, this tryptophan will be converted to toxic metabolites such as hydroxikynurenine, xanthurenic acid and hydroxyanthranilic acid, by the liver. 

Now assuming that tryptophan was successfully converted to the 5HT compound without being lost as Vitamin B3 or toxin metabolites or both, it now faces competition with 5 other amino acids (tyrosine, valine, leucine, isoleucine and phenylanine) to reach the blood-brain barrier. 5HT is carried to the barrier through carbohydrate transport molecules. What can be done at this stage, is to make more carbohydrate available so that the chances of tryptophan transportation increase. A migraineur’s preference should be a mild increase in the intake of complex carbs (wholemeal grains, cereals, lentils, pulses etc). This makes free buses available to carry the tryptophan to the brain.

Crossing the blood brain barrier and reaching the Central Nervous System, 5HT is converted to serotonin. 

Doctors prescribe 5HTP supplements as they have better chances to convert to serotonin than tryptophan supplements. It is generally also prescribed with a low dose of Vitamin B3 and B6. The indicative doses are generally in the range of 1 -3 grams of tryptophan, 100 mg of B3 and 25 mg of Vitamin B6.  Consult your doctor before taking them.

Next week I shall touch upon the importance of serotonin and how it helps alleviate symptoms of disturbed sleep, depression etc in migraineurs.

Until then, take care.

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Tryptophan in Tackling the Terrible Times

Hi,

Tryptophan today is often written and talked about as an essential amino acid, which doubles up as a precursor to the all important serotonin ( a polypeptide neurotransmitter).

Migraineurs are known to be defecient in serotonin levels and this defeciency is known to be a major factor in triggering migraines. However, serotonin cannot be taken as a supplement as it is not permitted through the blood-brain barrier to enter the brain, where it is required. Studies have found that if we increase the intake of tryptophan-rich foods, then we increase the level of serotonin from a state of deficiency in migraineurs. 

Some tryptophan-rich foods are spirulina, cod, peas, soya, pulses, salmon, beans, egg whites, turkey, cottage cheese, tofu, sesame seeds, avocados and all types of beans (fava, lima, kidney, pinto, broad etc). 

The process of conversion and metabolization of tryptophan to serotonin is a 3 stage process and is greatly helped by the presence of adequate levels of Vitamin B3 and B6 in our body. 

The tryptophans are large molecules (see image below) and their break down and absorption is not as easy as those of the smaller molecule amino acids. To divert the small molecule amino acid such that they do not compete with the absorption of tryptophan, we must marginally increase our insulin levels. This should not be done by intake of sugar, but through mildly increasing the intake of brown rice, bran bread, oat porridges and jacket potatoes. Refined sugar should not be a part of the diet of a migraineurs, preferably even in small doses.

The Wikipedia Common image gives the structure of a tryptophan molecule:

     

The conversion of tryptophan to serotonin and eventually to melatonin is exhibited beautifully in the following link: http://en.wikipedia.org/wiki/File:Tryptophan_metabolism.png

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Calcium’s Control on Serotonin Channels

Hi,

Much as Magnesium’s role in migraine management has been spoken about, Calcium has almost always figured as an also-ran. But Calcium intake, it’s effective metabolisation and absorption are just as important as Magnesium balance in your food.

Calcium is known to have anti-spasmodic action, which helps alleviate headaches and migraines. However, studies have shown that when calcium is administered along with Vitamin D, it reduces the frequency of migraines in a considerable number of patients .

Recent studies have also concluded that abnormalities in the channels within the cells that transport calcium, magnesium, sodium and potassium contribute to the onset of migraines. The calcium channels are known to regulate the release of serotonin. With impaired functioning of the channels, serotonin may not be effectively released or may be released in low quantities. This would contribute towards migraine occurrences.

For Reader’s Interest – a related link: http://mcb.berkeley.edu/labs/zucker/PDFs/Wang_Neuron21,155.pdf

The RDA for Calcium in women of the age group 18- 50 is approximately 1000 mg and between 1000-1300 mg for pregnant and lactating women. For post-menopausal women the RDA is set at about 1500 mg.
Calcium absorption reduces with aging and is dependent on a variety of factors such as genetics, availability of Vitamin D, intake of Vitamin C among others.

However, any supplement or drug should be had with consultation with your physician. Self-medication is a dangerous practice and can have fatal outcomes.

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