P5P

p5p

P5P is also known as pyridoxal 5?-phosphate, and is one of the six active forms of vitamin B6. (1) When ingested, vitamin B6 undergoes processing in the liver and becomes active and available to support hundreds of enzymatic reactions. (2) P5P specifically serves as a coenzyme in the metabolism of many important processes and larger systems of the body, and is largely considered the most important active form of vitamin B6.

Vitamin B6 is water-soluble and not made or stored in the body. To maintain normal levels of vitamin B6 in the body, it is necessary to continually supply the body with foods or supplements that contain vitamin B6. However, taking a P5P supplement seeks to bypass the intermediary step of activation, making it immediately bioavailable. There is no known natural source of P5P, which means supplementation is the only available source for this active form of vitamin B6.

Once P5P is present in the body, it seeks to support many healthy functions, including:

  • Amino acid metabolism
  • Blood sugar metabolism
  • Metabolism of fats
  • Hemoglobin synthesis
  • Oxygen transport in red cells
  • Iron, magnesium, and folate synthesis
  • Hormone production and regulation
  • DNA expression
  • Learning, memory, focus
  • Normal mood and behavior
  • Pregnancy
  • Immune system
  • Cardiovascular system
  • Liver and detoxification
  • Normal water retention
  • Temporary relief from occasional symptoms associated with beriberi, diabetic neuropathy, scurvy, pellagra, anemia when combined with a healthy diet that includes vitamins(3)
  • ... and more than 100 other functions in organs, biological systems, or as a cofactor in enzymatic reactions

Our understanding of the many roles that vitamin B6 plays in the body is relatively new. In fact, it was not until the early 1900s that scientists first identified the structures of vitamins. In the decades that followed these discoveries, new research shed light on both the sources of nutrients and how they function within the body.

The History of Vitamins

Over the course of human history, millions have relied on a diet consisting mostly of grains or in some more rare cases salted meats. These foods provide a high caloric value and store well during winter months and long voyages across the sea, but they lack the vitamins that are found in fruits and vegetables. Due to the lack of refrigeration or the ability to transport fruits and vegetables long distance without spoiling, people could go for long months without any of these foods. This lack of food diversity is known to result in diseases such as scurvy, pellagra, anemia, and beriberi. Each of these conditions affects different areas of the body and can ultimately lead to death.

Unfortunately, combating these deficiencies was nearly impossible because our understanding of vitamins has been limited for most of human history. It wasn’t until the 1860s that scientists first theorized the existence of germs. Once this discovery was made, attempts were made to link pathogens to the conditions that result from nutritional deficiency, assuming that microbes must be the cause. Only a few decades later, however, the word of chemists and physiologists began to identify vitamins for what they are.

Thiamine: The First B Vitamin

In 1889, the Dutch physician Christiaan Eijkman sought to understand why the beriberi epidemic was common in areas where people primarily ate a diet of refined rice. (4) Using chickens as a test model, he fed one group of chickens machine polished white rice and the other group brown rice. (5) The chickens that ate the white rice soon developed symptoms of beriberi, while the brown rice group did not. Eijkmans colleague Gerrit Grijns would later advance this study by proposing that the bran in brown rice might be somehow connected to the health of the chickens.

Following the rice test models, in 1906, the biochemist Frederick Gowland Hopkins conducted his own test. At this point, it was recognized that nutrition and diseases like beriberi and scurvy might be connected. In his model, animals were fed purified fats, proteins, and carbohydrates. The study revealed that this combination, while perceived as a hearty diet of that time, failed to keep animals healthy. From these results, Gowland would propose that there must be "accessory food factors" that provide essential nutrients.

By 1911, the state of nutrition started to come into focus when the Polish biochemist Casimir Funk proposed the existence of an unknown organic substance that he named "vitamines," which combines "vital" with "amine," a nitrogen-containing group in organic molecules. He suggested that in small amounts, these vitamines would help to maintain health. Eventually, researchers would discover that not all vitamins possess amine structures, but due to the popularity of the term, only the "e" was dropped.

Later in 1913, a biochemist at the University of Wisconsin, Elmer McCollum, determined there are two different species of vitamins, known as "fat-soluble factor A" and "water-soluble factor B." This sparked a worldwide interest in this area of research. After decades of study, in 1926, the Dutch chemists Barend Jansen and Willem Donath isolated a compound that had anti-beriberi factors. This compound was later named vitamin B1, or thiamine.

Vitamin B6 - Pyridoxine

After the discovery of several major B vitamins by other scientists, in 1934, Paul György and his colleagues in Germany discovered vitamin B6 (pyridoxal 5'-phosphate; P5P).(6) The active compound, P5P, was first isolated by Samuel Lepovsky, of the University of California, Berkeley, in 1938. A year later in 1939, Karl Folkers and the Merck company determined the structure of vitamin B6, which furthered the understanding of vitamin B6 and its potential benefits on the health of individuals.

p5p infographic

Potential Vitamin B6 and P5P Benefits

As noted previously, vitamin B6 is an essential nutrient that supports many different functions in the body. But, vitamin B6 is not stored for extended periods of time inside the body. Instead, unused vitamin B6 moves through the bloodstream and is eventually filtered out by the liver. When vitamin B6 is no longer present in the body, a nutritional deficiency can occur and disrupt feelings of health and wellness. When present in normal amounts, research has found that vitamin B6, and its six active forms, such as P5P, support the body in several ways.

Inflammation

In a study that examined plasma levels of pyridoxal 5'-phosphate and systemic markers of inflammation in adults, researchers gathered data from a total of 3539 participants between 1971 and 2001. Analysis of each participant occurred every 3 to 8 years.(7)

The study proposed that "low vitamin B-6 status, marked by low concentrations of plasma pyridoxal-5?-phosphate, has been identified as a risk factor for cardiovascular disease (CVD) morbidity and mortality, including myocardial infarction, atherosclerosis, and stroke. Patients with confirmed CVD often present with lower P5P plasma concentrations compared with healthy controls. Low plasma P5P is also seen in patients with rheumatoid arthritis, inflammatory bowel disease, and diabetes."

During testing, researchers used commercially available enzyme-linked immunoassay kits to take fasting blood samples. Multiple analysis were conducted and compared against the health status of each patient. The status of each patient included "age; sex; BMI; plasma homocysteine, folic acid (vitamin b9), and vitamin B12; serum creatinine and total cholesterol; vitamin B-, protein, and energy intakes; multivitamin supplement and NSAID use; and current smoking status."

In the conclusion of the study, researchers write that there appears to be a relationship between the amount of vitamin B6 in the body and inflammation. Specifically, as inflammation increases, vitamin B6 levels decrease. Interestingly, the study found that inflammation has no association with a change of vitamin B9 and B12, which were also part of the study. This seems to indicate that vitamin B6 levels may be a good indicator of inflammation in the body. While the data seems to support the researcher's hypothesis, the study goes on to note that "further studies on the mechanism of the relationship between PLP and inflammation are clearly warranted."

Immune System

To investigate the possible effects of vitamin B6 for support of the immune system, researchers in Taiwan performed a study with 51 subjects in the intensive care unit of the Taichung Veterans General Hospital, in Taichung.(8) Each patient was assigned to one of three groups and received a vitamin B6 injection of 50 mg, 100 m, or a placebo. Over the course of the study, levels of active B6 compounds, serum albumin, hemoglobin, hematocrit, high-sensitivity C-reactive protein, and immune responses in urine were measured.

The results show that in the two groups given a vitamin B6 injection, immune response factors found in urine increased "significantly" by the 14th day. The increase of immune factors found in urine indicates that body's production or immune response could be linked to levels of vitamin B6 in the body.

Brain and Cognition

To better understand the role of B vitamins in the body, the Brain, Performance and Nutrition Research Centre, at Northumbria University, in Newcastle, England, provides an analysis of how B vitamins, such as vitamin B6, affect the brain.(9)

The research notes that one of the many roles of vitamin B6 in the brain is to help metabolize amino acids that are necessary for the synthesis of neurotransmitters such as dopamine, serotonin, GABA, noradrenaline, and melatonin. When a vitamin B6 deficiency occurs, it has been shown to affect cognition, which can include “sleep, behavior, cardiovascular function, and a loss of hypothalamus-pituitary control of hormone excretion." Additionally, vitamin B6 has a "direct effect on immune function and gene transcription/expression and plays a role in brain glucose regulation." The function of vitamin B6 may also extend to numerous pathological states, which include "dementia and cognitive decline."

Additionally, the research notes that many studies have examined the relationship between B vitamins and homocysteine, an amino acid that is a product of protein metabolism and has been linked to cardiovascular challenges and cognitive decline. It is believed that vitamin B6, B9, and B12 play a role in the regulation of homocysteine concentrations found in the blood. Therefore, these vitamins may support the brain and possibly the cardiovascular system during normal aging. However, understanding how B vitamins may support the brain or cardiovascular system is not entirely understood. In fact, making claims about these potential benefits has prompted criticism, and a call for further studies to demonstrate clearer results.

Healthy Joints

Adequate levels of vitamin B6 in the body is known to help prevent some nerve-related conditions, such as beriberi. However, vitamin B6 is now being examined as a possible treatment for carpal tunnel syndrome (CTS). (10) Research from the College of Family Physicians of Canada suggests that while supplementation may support CTS as a result of an underlying nerve condition that results from a vitamin B6 deficiency, it might also work to provide comfort due to evidence that shows it helps to raise the pain threshold.

In the same research, it is noted that patients with CTS undergoing treatment with 100 mg of vitamin B twice daily reported an alleviation of symptoms that was 68% higher than patients that did not. However, the study involved examining patient charts, and as a result, no firm conclusion can be made. It is suggested that for patients undergoing CTS treatment, a combination of nonsteroidal anti-inflammatory drugs, nighttime splinting, ergonomic workstation review, and 200 mg of vitamin B6 daily may be beneficial.

Vitamin B6 and P5P Dosing

When looking at the Recommended Dietary Allowances (RDAs) of vitamin B6, the intake levels represent the amount of vitamin B6 that is sufficient for at least 97% of individuals. (11) Currently, there is no established dosing guidelines for P5P or the other active forms of vitamin B6, so follow the same guidelines as vitamin B6. Exceeding the RDA may result in adverse health effects and therefore higher dosing should be discussed with a health practitioner. Daily requirements may vary depending on individual health and prescribed or OTC medications.

Recommended Dietary Allowances For Vitamin B6

Insert Table 1 Image Here https://docs.google.com/spreadsheets/d/150EfrUWL_k9h2n0UFboyM61hfSRkX1IWX5P7_7J4aPk/edit#gid=0

There are no well established side effects of high intakes of vitamin B6 from food sources. However, the National Institutes of Health notes that the administration of 1000 to 6000 mg of vitamin B6 as an oral supplement each day for 12–40 months can cause severe and progressive sensory neuropathy, and painful, disfiguring dermatological lesions; photosensitivity; and gastrointestinal symptoms, such as nausea and heartburn. If any of these symptoms occur in smaller doses, immediately stop taking the supplement and consult a healthcare professional.

Tolerable Upper Intake Levels For Vitamin B6

Insert Table 2 Image Here - https://docs.google.com/spreadsheets/d/150EfrUWL_k9h2n0UFboyM61hfSRkX1IWX5P7_7J4aPk/edit#gid=0

Not all vitamin B6 and P5P supplements are formulated the same way, with some supplements containing additional vitamins, herbs, and extracts that might alter the effect of vitamins in the body. Vitamin B6 is available from many natural food sources, and is believed to have a 75% bioavailability, which makes it relatively efficient when seeking to fill nutritional needs during the day. Some foods that may be ideal include:

  • Chickpeas
  • Beef liver
  • Tuna or yellowfin
  • Salmon
  • Chicken breast
  • Fortified breakfast cereals
  • Potatoes
  • Turkey meat
  • Banana
  • Marinara sauce
  • Ground beef
  • Waffles
  • Cottage cheese
  • Squash
  • Enriched rice
  • Nuts
  • Raisins
  • Onions
  • Spinach
  • Tofu
  • Watermelon

Vitamin B6 content might not be labeled on food as the FDA does not require food labels to list vitamin B6 content unless food has been fortified with this nutrient. If food intake is not enough to meet daily recommended levels of nutrients, then supplementation may be ideal.

Begin a Vitamin B6 or P5P Regimen!

Vitamin B6 or P5P supplements can help to fill nutritional gaps to more effectively meet daily dietary needs. Supplements with these nutrients are available in many forms, including capsule, tablet, powder, and sometimes liquids. Whether dietary restrictions limit food choice, or additional support is needed during internal challenges, vitamin B6 or P5p may help you to achieve feelings of health and wellness.

Today, we understand that eating a mix of carbohydrates, proteins, fats, vitamins, and minerals will provide the body with the compounds it needs to function normally. Even if certain foods aren't available, modern innovations such as supplementation make it easy to meet dietary needs. Of course, none of this would be possible without the work of scientists who finally identified and discovered the function of vitamins in the body.

Sources

  1. https://www.nap.edu/read/6015/chapter/9#151
  2. http://www.sciencedirect.com/topics/neuroscience/pyridoxal-phosphate
  3. http://ispub.com/IJNW/1/1/9970
  4. https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/vitamin-b-complex.html
  5. https://www.nobelprize.org/nobel_prizes/themes/medicine/carpenter/
  6. http://isrhml.net/awards/macy-gyorgy/paul-gyorgy
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374666/
  8. https://www.ncbi.nlm.nih.gov/pubmed/16670691
  9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1949298/
  11. https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/