Wednesday, 1 August 2012

Lucid dream supplements (3) - Vitamin B6

* Vitamin B6 – composition & function
Vitamin B6 is a water-soluble compound, discovered in the 1930s during laboratory experiments and various nutrition studies, performed on rats. In 1934, Hungarian physician, Paul György discovered a substance that was able to cure a skin disease in rats (known as dermititis acrodynia) which he named ‘Vitamin B6’. In 1938, Samuel Lepkovsky isolated Vitamin B6 from rice bran. In 1939 Harris and Folkers determined the structure of pyridoxine, and, in 1945, Snell was able to show the two forms of Vitamin B6, pyridoxal and pyridoxamine. Vitamin B6 was named pyridoxine to indicate its structural homology to pyridine. All three forms of Vitamin B6 are precursors of an activated compound known as ‘pyridoxal 5'-phosphate’ (PLP), which plays a vital role as the cofactor of a large number of essential enzymes in the human body. Enzymes dependent on PLP focus a wide variety of chemical reactions mainly involving amino acids. The reactions carried out by the PLP-dependent enzymes that act on amino acids include transfer of the amino group, decarboxylation, racemization, and beta or gamma elimination/replacement. Such versatility arises from the ability of PLP to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates. The term “Vitamin B6” therefore refers to a group of chemically similar compounds which are metabolically interchangeable: pyridoxine (the alcohol form), pyridoxal (the aldehyde form), and pyridoxamine (the amine form). Most Vitamin B6 supplements come in the pyridoxine form as it is most active and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation and assists in the proper metabolism of carbohydrates, fats and proteins It plays a role in synthesising RNA (Ribonucleic acid - part of a group known as ‘nucleic acids’) and DNA; and cell multiplication. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen and the proper absorption of Vitamin B12, selenium, calcium and magnesium. Vitamin B6 metabolises in the liver. 

The main functions of Vitamin B6 are:
  • amino acid, glucose and lipid metabolism
  • neurotransmitter synthesis
  • histamine synthesis
  • haemoglobin synthesis and function
  • gene expression
  • facilitates decarboxylation, transamination, racemisation, elimination, replacement and beta-group interconversion reactions 

* Vitamin B6 deficiency
By not consuming a sufficient amount of B6 in your diet, you could be at risk of Vitamin B6 deficiency, which manifests in symptoms such as tongue inflammation, irritability, fatigue, weakness and scale-like formations on the skin and mouth. It can also lead to depression and, in severe cases, seizures. The classic clinical syndrome for Vitamin B6 deficiency is a seborrhoeic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis, conjunctivitis, intertrigo, and neurologic symptoms of somnolence, confusion, and neuropathy. A deficiency of Vitamin B6 alone is relatively uncommon and often occurs in association with other vitamins of the B complex. The elderly and alcoholics have an increased risk of Vitamin B6 deficiency, as well as other micronutrient deficiencies. Renal patients undergoing dialysis may experience Vitamin B6 deficiency. Also, patients with liver disease, rheumatoid arthritis, women with Type 1 diabetes and those infected with HIV also appear to be at risk, despite adequate dietary intakes. The availability of Vitamin B6 to the body can be affected by certain drugs such as anticonvulsants and corticosteroids. The drug isoniazid (used in the treatment of tuberculosis), and cycloserine, penicillamine, and hydrocortisone all interfere with Vitamin B6 metabolism. These drugs may form a complex with Vitamin B6 that is inhibitory for pyridoxal kinase, or they may positively displace PLP from binding sites.

* Sources of Vitamin B
Vitamin B6 is commonly found in food sources, in both its ‘free’ and ‘bound’ forms. Good dietary sources of Vitamin B6 are meat (liver/kidney, chicken, turkey pork and beef); bananas; dairy produce and eggs; vegetables (especially leafy greens such as kale, broccoli, spinach, chard, Brussels sprouts cabbage etc, asparagus, cauliflower, celery, green peas, potatoes – particularly the skin, yams, carrots and bell peppers); fish (tuna, salmon, halibut, trout, snapper and cod); nuts (peanuts, cashews, sunflower seeds and hazelnuts); Brewer’s yeast; wholegrains and bran; beans and legumes (chickpeas, lentils and soya beans). It is normal for the average person with a healthy diet to consume their recommended daily intake of Vitamin B6 in dietary form, without the need to resort to supplements. However, it should be noted that storage, processing and cooking of food products can result in up to 50% of the Vitamin B content being lost. Vitamin B6 supplements – either on their own, or as part of a Vitamin B complex formulation – are readily available for general purchase in pharmacies, health stores and supermarkets. I use Holland & Barrett (a B-complex formula) as I know I can rely on the quality of their products. 

Vitamin B6 is absorbed in the jejunum and ileum via passive diffusion. With the capacity for absorption being so great, animals are able to absorb quantities much greater than what is needed for physiological demands. The absorption of pyridoxal phosphate and pyridoxamine phosphate involves their dephosphorylation catalysed by a membrane-bound alkaline phosphatase. Those products and non-phosphorylated vitamers in the digestive tract are absorbed by diffusion, which is driven by trapping of the vitamin as 5'-phosphates through the action of phosphorylation (by a pyridoxal kinase) in the jejunal mucosa. The trapped pyridoxine and pyridoxamine are oxidized to pyridoxal phosphate in the tissue. The products of Vitamin B6 metabolism are excreted in the urine; the major product of which is 4-pyridoxic acid. It has been estimated that 40 - 60% of ingested Vitamin B6 is oxidized to 4-pyridoxic acid. Several studies have shown that 4-pyridoxic acid is undetectable in the urine of Vitamin B6 deficient subjects, making it a useful clinical marker to assess the Vitamin B6 status of an individual. Other products of Vitamin B6 metabolism that are excreted in the urine when high doses of the vitamin have been given include pyridoxal, pyridoxamine, and pyridoxine and their phosphates. A small amount of Vitamin B6 is also excreted in the faeces.

* Toxicology
With regard to toxicology, adverse effects have only been documented from Vitamin B6 supplements and never from food sources alone. This article only discusses the safety of the common supplemental form of Vitamin B6, pyridoxine. Toxicologic animal studies identify specific destruction of the dorsal root ganglia, which is documented in human cases of overdosage of pyridoxine. Although it is a water-soluble vitamin and excreted in the urine, doses of pyridoxine in excess of the RDI over long periods of time result in painful and ultimately irreversible neurological problems. The primary symptoms are pain and numbness of the extremities of the body, such as fingers and toes, and in severe cases, difficulty walking. Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day. However, a few individuals who developed sensory neuropathies at doses of less than 500 mg daily over a period of months have been reported. None of the studies, in which an objective neurological examination was performed, found evidence of sensory nerve damage at intakes below 200 mg/day. This condition is usually reversible when supplementation is stopped. Existing authorisations and valuations vary considerably worldwide. In 1993, the European Community Scientific Committee on Food defined intakes of 50 mg of Vitamin B6 per day as harmful and established a tolerable upper intake level of 25 mg/day for adults in 2000. The Expert Group on Vitamins and Minerals of the Food Standard Agency UK (UK EVM) derived a safe upper level (SUL) of 10 mg/day for a 60-kg adult in 2003. The tolerable upper limit has been set by the US FDA at 100 mg/day in 2000. The nutrient reference values in Australia and New Zealand recommend an upper limit of 50 mg a day in adults. The same figure was set for pregnancy and lactation as there is no evidence of teratogenicity at this level. The UL was set based on metabolic body size and growth considerations for all other ages and life stages, except infancy. It was not possible to set a UL for infants, so intake is recommended in the form of food, milk or formula only. The ULs were set using results of studies involving long-term oral administration of pyridoxine at doses of less than 1g/day (Berger & Schaumburg 1984, Bernstein & Lobitz 1988, Dalton 1985, Dalton & Dalton 1987, Del Tredici et al 1985, Parry & Bredesen 1985). A NOAEL of 200 mg/day was identified from the studies of Bernstein & Lobitz (1988) and Del Tredici et al (1985). These studies involved subjects who had generally been on the supplements for 5 - 6 months or less. The study of Dalton and Dalton (1987), however, suggested the symptoms might take substantially longer than this to appear. In this latter retrospective survey, subjects who reported symptoms had been on supplements for 2.9 years, on average. Those reporting no symptoms had taken supplements for 1.9 years. Because no placebo-controlled studies show therapeutic benefits of high doses of pyridoxine, and the well-documented occurrence of significant toxic effects, there is little reason to exceed the RDI using supplements unless under medical supervision i.e. in treatment of primary hyperoxaluria.

* Medicinal/therapeutic use
Vitamin B6 has been used to treat nausea and vomiting in early pregnancy for decades, commonly in conjunction with other medications such as metoclopramide or doxylamine. Alone, it has been found safe and effective, though any woman's prenatal caregiver must help guide treatment for these symptoms. The intake of Vitamin B6, from either diet or supplements, could cut the risk of Parkinson's disease by half according to a prospective study from the Netherlands, although it has since been argued that this association was restricted to smokers, and the vitamin is known to increase the metabolism of other medication given in the treatment of Parkinson’s, such as levodopa. Pyridoxine has a role in preventing heart disease. Without enough pyridoxine, the compound homocysteine builds up in the body, causing damage to blood vessel linings and setting the stage for plaque build-up when the body tries to heal the damage. Vitamin B6 prevents this build-up, thereby reducing the risk of heart attack. Pyridoxine lowers blood pressure and blood cholesterol levels and keeps blood platelets from sticking together. All of these properties work to keep heart disease at bay. Nutritional supplementation with high dose Vitamin B6 and magnesium is one of the most popular alternative medicine choices for autism, but randomised control trials have had mixed results and small sample sizes mean no conclusions can be drawn as to the efficacy of this treatment. Some studies suggest the Vitamin B6-magnesium combination can also help attention deficit disorder, citing improvements in hyperactivity, hyperemotivity/aggressiveness and improved school attention. A lack of the vitamin may play a role in sensitivity to monosodium glutamate (MSG), a common flavour enhancer, often used in processed foods. This sensitivity can cause headaches, pain and tingling of the upper extremities, nausea, and vomiting. In both of these syndromes, supplementation of pyridoxine alleviates symptoms only in people already deficient in the vitamin. If people are marginally deficient in Vitamin B6, they may be more susceptible to carpal tunnel syndrome (CTS). CTS is characterised by pain and tingling in the wrists after performing repetitive movements or otherwise straining the wrist on a regular basis. Vitamin B6 has been shown in at least two small-scale clinical studies to have a beneficial effect on the syndrome, particularly in cases where no trauma or overuse etiology is known. Vitamin B6 has long been publicised as a cure for premenstrual syndrome (PMS). Study results conflict as to which symptoms are eased, but most confirm women who take B6 supplements have reductions in bloating, breast pain, and premenstrual acne flare, a condition in which pimples break out about a week before a woman's period begins. Strong evidence suggests pyridoxine supplementation, starting 10 days before the menstrual period, prevents most pimples from forming. This effect is due to the vitamin's role in hormone and prostaglandin regulation. Skin blemishes are typically caused by a hormone imbalance, which Vitamin B6 helps to regulate. Mental depression is another condition which may result from low Vitamin B6 intake. Because of pyridoxine's role in serotonin and other neurotransmitter production, supplementation often helps depressed people feel better, and their moods improve significantly. It may also help improve memory in older adults However, the effectiveness as treatment for PMS, PMDD, and clinical depression is debatable. 

Ingestion of Vitamin B6 possibly can alleviate some of the many symptoms of an alcoholic hangover, which might be due to its mild diuretic effect. Though the mechanism is not known, results show pyridoxamine has therapeutic effects in clinical trials for diabetic nephropathy. Larsson et al. have shown Vitamin B6 intake and pyridoxal phosphate (PLP) levels are inversely related to the risk of colon cancer. While in their study the correlation with B6 intake was moderate, it was quite dramatic with PLP levels, where the risk of colon cancer was nearly decreased by half.

* Vitamin B6 & effects on dreaming
Importantly, Vitamin B6 has been shown in a number of studies to have an influence on dreaming. A 2002 double-blind study of 12 college students (4 participants took 250mg, 4 took 100mg and 4 were given placebos) by Ebben, Leqeurica & Spielman (of City College, New York) demonstrated that taking 250 mg of Vitamin B6 daily, over a period of 5 days, caused a significant difference in dream content (as rated by the participants), in the areas of: dream vividness, emotionality, bizarreness and colour. However, most studies on the correlation between Vitamin B6 ingestion and effects on dreaming suggest that a dose of 250mg is required in order to cause such results – this being considerably higher than many RDI dosages, as quoted above. This should be qualified with the fact that anecdotal evidence, mined from online sources such as specialist webpages/Blogs and forums/message-boards, indicates some amateur dreamers claims effects after ingesting quantities of Vitamin B6, ranging from 50 – 500 mg daily. In moderate toxicity, Vitamin B6 has been shown to increase the ability to recall dreams. 

The data for dream salience suggests that Vitamin B6 may act by increasing cortical arousal during periods of rapid eye movement (REM) sleep. A hypothesis is presented involving the role of B6 in the conversion of tryptophan to serotonin. Tryptophan is an essential amino acid which the body metabolises into serotonin and niacin.

Tryptophan is found in abundance in shrimp, soy sauce, tuna, spinach, soya beans, eggs, bananas, shellfish, turkey, red meat, nuts and seeds. Low levels of tryptophan is associated with poor dream recall.

The small volume of scientific research into Vitamin B6 and lucid dreaming does not find any significant relationship, although anecdotal evidence from oneironauts (dream-explorers) suggests that Vitamin B6 has in fact assisted some people in becoming lucid in their dreams. 

This perceived effect may be explained in the following way. During REM sleep protein-synthesis is highly active, so your body needs high levels of amino acids. The neurotransmitter in use during REM sleep is acetylcholine. It is made from the B vitamin choline and the Vitamin B5. The body can synthesis the B vitamin choline, but in order to do that it needs Vitamin B12, folic acid (Vitamin B9), the amino acids. methionine and serine. Vitamin B12 plays a role in the activation of amino acids during protein formation. It has also the ability to increase the production of acetylcholine and normalise neurotransmissions in the brain (see above). Vitamin B6 is an important vitamin as it is a co-enzyme, which participates in over 60 enzymatic reactions involved in the metabolism of amino acids (see above) and is involved in the production of several body proteins and neurotransmitters. It is particularly indispensable to the action of amino acid neurotransmitters, like serotonin, dopamine, melatonin, and norepinephrine, which effect brain function – and all of which have been studied or discussed in relation to their impact upon dreaming. Melatonin is a neurotransmitter/hormone that is only active during sleep. It is being metabolised when you fall asleep from serotonin, a neurotransmitter that is, in turn, metabolised from the amino acid tryptophan. Melatonin increases non-REM sleep and makes it easier for you to fall asleep, but it has also an interesting rebound effect that gives more frequent and vivid dreams, which may result in an increase in lucidity also. The amino acid tryptophan can be metabolised into serotonin and niacin (Vitamin B3) - Vitamin B6 promotes this conversion. Taking niacin or nicotine patches will increase the serotonin production and thus, the more niacin you take, the more serotonin is produced and consequently, melatonin, is metabolised. Calcium and magnesium promotes serotonin production also and there is some suggestion that zinc (which is in every cell of the body and is a part of over 200 enzymes) may increase REM-sleep, too. DMAE (Dimethylaminoethanol) is a very important B vitamin. It flows easily through the brain's blood barrier, where it is converted into choline. During REM sleep, choline is added the co-enzyme A (Vitamin B5), and we have acetylcholine, the neurotransmitter in use during REM sleep. The blood brain barrier makes taking serotonin by itself is largely ineffective in dream exploration, and therefore Vitamin B and tryptophan have the advantage of being metabolised within the body and sent directly to the brain. Tryptophan is found in such foods as cheese, chicken, salmon, lamb, egg, flour, white rice, and milk. Cheddar cheese has the most amount of tryptophan, and is recommended highly as a dietary source. The effect of increased tryptophan as a result of consuming cheese – and the consequent effects on dreaming – is the likely source of the ‘myth’ that eating cheese before bed causes nightmares or dreams. If wanting to experiment with the effect of Vitamin B6 on dreaming, it is recommended that you take any supplements just prior to going to bed. If you intend to increase your Vitamin B intake through dietary sources alone, continue to eat at normal times, but try to consume some cheddar cheese shortly before bed, for the reasons stated above.

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