VITAMIN B6
Vitamin B6, also known as pyridoxine, is an essential nutrient that is required for many critical functions in the body. It is one of the B-vitamins, used in producing a necessary coenzyme in the body. Despite its importance, vitamin B6 deficiency is relatively rare, as it can be found in many common foods such as fish, poultry, potatoes, and bananas. However, the popularity of vitamin B6 supplements has increased in recent years, with many people turning to this nutrient as a way to boost their overall health and wellness.
While vitamin B6 does have many small benefits, such as supporting the immune system and aiding in the metabolism of protein and carbohydrates, there appear to be no highly effective unique reasons to use this supplement. In this article, we will explore the various benefits and limitations of vitamin B6 supplementation, including its potential uses in preventing and treating certain medical conditions, as well as the risks and side effects associated with excessive intake.
By understanding the science behind vitamin B6 and its role in the body, you can make an informed decision about whether or not to incorporate this supplement into your diet. So, let’s dive in and explore the potential benefits and drawbacks of vitamin B6 supplementation.
Sources & Composition
Vitamin B6 is actually a group of molecules known as vitamers, which share a similar structure to pyridoxine. Once consumed, these vitamers are converted to pyridoxal 5′-phosphate (PLP), which is the active form of the vitamin in the human body. PLP is essential for various bodily functions and is considered a crucial vitamin.
PLP primarily serves as a coenzyme in the human body, similar to essential minerals like zinc. Adequate amounts of PLP are necessary to enable the proper functioning of specific enzymes. PLP is involved in the functioning of enzymes that primarily regulate cellular proliferation. Low levels of vitamin B6 in the blood have been linked to some cancerous conditions that involve abnormalities in cellular proliferation and regulation. [1, 2, 3]
Dietary forms of vitamin B6 include:
- Pyridoxine
- Pyridoxal
- Pyridoxamine
Upon absorption in the intestine, dietary or supplemental forms of B6 are converted into the active form, pyridoxal 5′-phosphate (PLP), in both the liver and intestines. PLP then binds to serum albumin, which transports it to peripheral tissues.
The three primary dietary forms of vitamin B6 (pyridoxine, pyridoxal, and pyridoxamine) undergo an initial step catalyzed by the enzyme pyridoxal kinase, which adds a phosphate group at the 5′ position. However, only pyridoxal undergoes this process to form PLP.
For pyridoxine and pyridoxamine, their respective products, pyridoxine 5′-phosphate and pyridoxamine 5′-phosphate, require an additional step catalyzed by the enzyme pyridox(am)ine phosphate oxidase to produce PLP.
PLP can be converted back into pyridoxal by PLP phosphatase. Additionally, this enzyme can convert pyridoxine-5′-phosphate back into pyridoxine. To produce the urinary metabolite 4-pyridoxic acid (4-PA), pyridoxal must first be converted by aldehyde oxidase. This conversion requires pyridoxal to be hydrolyzed back into its original form. 4-PA is the final product of vitamin B6 metabolism.
Absorption
Early research suggested that pyridoxine hydrochloride, [1] pyridoxal (including its phosphate form), and pyridoxamine (as well as its phosphate) were absorbed through passive diffusion in rats.
In studies using isolated intestinal cells (Caco-2), researchers have found evidence of a saturable transporter that depends on concentration and pH. This transporter is capable of absorbing PLP and pyridoxamine in humans. In contrast, a colonic transporter does not appear to take up PLP. Furthermore, neither transporter appears to be capable of uptaking pyridoxamine. [1]
In tests conducted with jejunal segments, researchers found that certain fiber types, such as cellulose, pectin, and lignan, did not influence absorption rates. However, when homogenized carrots were introduced at a concentration of 1-3% of the medium, absorption of pyridoxamine and pyridoxal was reduced, but not that of pyridoxine.
Research suggests that a synthetic solution of pyridoxine is more bioavailable than a similar dose administered through orange juice. Interestingly, the addition of sugar to the synthetic solution can enhance its bioavailability when administered through intrajejunal infusion.
Main Takeaway: According to current understanding, there are specific transporters for various vitamin B6 vitamers that can absorb pyridoxamine. In the jejunum, which is the main site of absorption in the intestines, pyridoxal-5′-phosphate may also be absorbed via these transporters.
Neurology
Pyridoxine-5′-phosphate (PLP) dependent enzyme, L-dopa decarboxylase, plays a vital role in the conversion of L-DOPA into active dopamine. Studies have shown that pyridoxine infusion increases the activity of this enzyme, particularly in the hypothalamus, and the actions of pyridoxine infusion parallel those of dopamine in relation to prolactin and growth hormone. Insufficient levels of PLP in the brain have been shown to impair the activity of this enzyme.
Rats that lack pyridoxine exhibit considerably lower levels of pyridoxal phosphate (PLP) and serotonin in the hypothalamus. This leads to decreased plasma prolactin levels. Administration of a 5-HT1A agonist improved plasma prolactin levels, suggesting that a deficiency in pyridoxine decreases the activity of this serotonin receptor in the hypothalamus.
The interaction of pyridoxine with L-dopa decarboxylase, leading to the production of dopamine and serotonin, has been suggested to contribute to the induction of dreams. Serotonin based drugs (such as SSRIs) have been noted to increase subjective dream intensity. Some researchers hypothesize that the increase in dream intensity and frequency associated with pyridoxine supplementation may be due to increased arousal during REM sleep, which is when dreams tend to occur most frequently, and subsequent awakening.
According to the study, when participants self-reported the intensity of their dreams after a night of sleep, the results showed that 100mg and 250mg pyridoxine resulted in dose-dependent increases in dream salience compared to the placebo group.
Obesity & Fat Mass
The dose-dependent reduction of intracellular calcium (12-36%) in 3T3-L1 adipocytes appears to be related to the increase of pyridoxal-5′-phosphate (PLP) concentration in the range of 50-100nM. Moreover, this reduction is accompanied by a decrease in fatty acid synthase (FAS) activity and expression.
The negative regulation of calcium signaling by pyridoxine in general is believed to be the reason for this, as well as the adipogenic effects of calcium in fat tissue. [1]
A study conducted on overweight individuals found that a combination of leucine (2.25g) and pyridoxine (30mg) supplementation resulted in a reduction of respiratory exchange ratio by 0.019 units. This decrease in respiratory exchange ratio is believed to lead to an increase in daily fat loss by 33.6g.
Interactions with Hormones
The activity of glucocorticoid receptors at the transcriptional level appears to be suppressed by higher concentrations of pyridoxal 5′-phosphate (PLP) in cells. [1]
To avoid plagiarism, you could write: When pyridoxine is absent from the medium, it can lead to a mild deficiency and increase the activity of the receptor by 98%. Conversely, a high concentration of pyridoxal 5′-phosphate (PLP) of 1,000 µM can suppress activity by 48%.
A study involving 10 healthy women who were administered 200mg of pyridoxine twice a day did not show any significant changes in cortisol or ACTH levels compared to their baseline measurements.
Lower concentrations of 1-100μM of pyridoxine did not demonstrate any effect on growth hormone secretion in primary rat pituitary cells, whereas a higher concentration of 1,000μM was found to inhibit growth hormone secretion from pituitary cells.
When given acutely to otherwise healthy women, supplementation of pyridoxine (200mg twice daily) did not lead to a significant increase in growth hormone secretion over 24 hours. However, there was a nonsignificant trend towards increasing nighttime growth hormone secretion.
During physical exercise and with an infusion of 600mg pyridoxine, the administration of the drug was linked to a greater increase in serum growth hormone levels during a cycling test. However, it is worth noting that the control group had slightly lower baseline serum pyridoxine levels, and a lower dose infusion of 300mg has been observed to increase growth hormone levels in acutely hospitalized individuals.
A decrease in vitamin B6 levels in rats leads to an elevation in plasma prolactin concentration.
Pyridoxal phosphate (PLP) has been shown to inhibit the proliferation of pituitary cells in vitro in different cell lines (MMQ, AtT-20, GH3) at concentrations ranging from 10-1,000μM without any toxicity, and in a reversible manner after removing PLP from the culture medium. This decrease in cell proliferation is linked to a reduction in hormone secretion. In primary rat pituitary cells, 1μM of PLP is able to decrease prolactin secretion to 66% of control (and 48% at 10μM), without affecting growth hormone secretion.
Main Takeaway: The overall effect of vitamin B6 on prolactin appears to be inhibitory. Inadequate intake of B6 can result in higher than normal serum prolactin concentrations, while increasing B6 intake has been associated with further suppression of prolactin.
Studies in rodents have shown that pyridoxine infusions can suppress increases in prolactin levels, such as those induced by chlorpromazine and opioids.
Acute supplementation of 200mg pyridoxine twice daily in women did not result in significant suppression of prolactin concentrations over the course of 24 hours, but there was a trend towards lower values relative to baseline.
Continuous infusion of 600mg pyridoxine has been observed to fully inhibit the increase in prolactin levels during exercise.
Interactions with Cancer Metabolism
In menopausal women, a study found an inverse relationship between serum pyridoxal-5′-phosphate (PLP) levels and breast cancer risk, with higher prediagnostic PLP levels associated with lower risk. Specifically, the highest quartile (greater than 116.6nM) had a 30% lower risk compared to the lowest quartile (less than 41.1nM).
The use of pyridoxine to alleviate hand-foot syndrome (HFS), a common side effect of the chemotherapy drug capecitabine that causes redness in the hands and feet, has been controversial and has yielded mixed results.
The use of pyridoxine for the management of Hand-foot syndrome (HFS), a common side effect of capecitabine chemotherapy, has been based on the similarity of symptoms between HFS and rat acrodynia caused by pyridoxine deficiency. A small pilot study administered 50-150mg pyridoxine after HFS developed in four out of five individuals receiving intravenous 5-fluorouracil and found beneficial effects on symptoms.
The administration of 150mg pyridoxine daily (50mg thrice daily) for 12 weeks in individuals with breast or colon cancer undergoing capecitabine therapy did not result in any significant reductions in symptom incidence, severity, or dose modification of capecitabine due to symptoms when compared to placebo. Although the study did not find a significant reduction in symptoms incidence, severity or dose modification of capecitabine due to symptoms with pyridoxine supplementation, there were some positive trends observed, especially for symptom severity. It is also noteworthy that pyridoxine had no effect on cancer.
Nutrient Interactions
COX inhibitors, such as aspirin and other NSAIDs, belong to a group of anti-inflammatory medications. Studies suggest that individuals using NSAIDs have lower levels of bioactive B6 (pyridoxal-5′-phosphate) than those not taking the drugs, and this decrease is more pronounced with prolonged usage. The decrease in PLP concentration was also observed in the liver and kidneys of rats and mice exposed to NSAIDs for extended periods of time.
ZMA is a blend of Zinc and Magnesium that is often combined with vitamin B6 and is named after the initial letters of these three components.
The natural 5α-reductase inhibitory effect of zinc, which could increase testosterone levels by decreasing its conversion to the androgen DHT, is observed at concentrations that are too high to be applicable to 15mM zinc supplementation in vitro. However, the addition of high concentrations of pyridoxine appears to lower the required amount of zinc for this effect to 1.5-3mM.
It is currently believed that this information is not applicable to dietary supplementation. This is because zinc supplementation has been associated with an increase in DHT, which occurs at the level of the 5α-reductase enzyme at a concentration of 500nM (0.5µM).
Safety & Toxicology
Pyridoxine neuropathy is a type of nerve damage caused by high doses of any vitamin B6 form, resulting in adverse symptoms such as sensory ataxia, reduced distal limb proprioception, paresthesia, and hyperesthesia. [1, 2] This condition is mostly observed in humans who have consumed doses exceeding 6,000mg for over one year.
One study observed negative effects at a dose as low as 200mg (which is 11,700% of the RDI and 200% of the TUL). However, in most animal studies where neuropathy was successfully induced, doses ranging from 50-300mg/kg were used [1, 2] (estimated human range of 27-162mg/kg and, for a 150lb person, at least 1.8g, similar estimated ranges from rat data). [1]
Two levels of toxicity have been observed with pyridoxine. The lower dose causes axonopathy, which is reversible upon discontinuation of pyridoxine, while the higher dose results in an irreversible sensory ganglion neuropathy. [1]
Main Takeaway: Taking high doses of vitamin B6 for a prolonged period of time can be highly toxic, leading to peripheral neuropathy that can be reversible or even irreversible sensory ganglion neuropathy. The toxic dose has been reported to be as low as 200mg (which is 11,700% of the recommended daily intake), while in humans, it is reliably induced at intake of around 5g (which is 300,000% of the recommended daily intake) or higher.
Summary
Tldr; The overall effect of vitamin B6 on prolactin appears to be inhibitory. Inadequate intake of B6 can result in higher than normal serum prolactin concentrations, while increasing B6 intake has been associated with further suppression of prolactin.
Taking high doses of vitamin B6 for a prolonged period of time can be highly toxic, leading to peripheral neuropathy that can be reversible or even irreversible sensory ganglion neuropathy. The toxic dose has been reported to be as low as 200mg (which is 11,700% of the recommended daily intake), while in humans, it is reliably induced at intake of around 5g (which is 300,000% of the recommended daily intake) or higher.
