By Karen Raterman
It’s no surprise that many Americans are overworked and highly stressed. A fast-paced lifestyle often leads to fast-paced eating which may include an overabundance of processed and refined foods. As a result, Americans are overweight and undernourished. Unfortunately, nutrient deficiencies are an increasingly common issue that has wide ranging implications for long-term health. One telling recent statistic now shows that close to 30 million Americans are deficient in vitamin B6, according the CDC’s Second National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population. This means that B6 is now one of the most prevalent deficiencies in the United States. Given its wide ranging functions in the body, especially regarding brain function and immunity, it is little wonder that there are also increasing rates of fatigue, depression and chronic levels of inflammation.1
Because B6 is often grouped with other B vitamins, it can be included in other more noted B-complex deficiencies, such as B12 and folic acid.2 As such, specific B6 deficiencies may not register for practitioners or patients. Isolated attention on this important nutrient is warranted especially when considering the rising rates of chronic health concerns. Emerging research continually finds links between vitamin B6 and issues around immune health and depression. Beyond that, a number of intriguing studies indicate the critical role of B6 for supporting women’s health issues, including reproductive health and the alleviation of PMS; athletic performance; and maintenance of healthy blood sugar levels.
The importance of B6
Vitamin B6 is a water-soluble vitamin, first isolated in the 1930s. It is the generic name for six compounds, though traditionally it is referred to in three vitamin forms: pyridoxal, pyridoxine, and pyridoxamine. The active coenzyme form, pyridoxal 5’ phosphate (PLP), has the most significance in the human metabolism.3 This compound has a variety of functions in the body, with involvement in more than 100 enzyme reactions primarily pertaining to protein metabolism.4,5 More specifically, PLP is involved in amino acid metabolism, as well as being specifically tied to absorption of carbon-units, carbohydrates, and lipids. PLP typically acts as a coenzyme for glycogen phosphorylase, which prompts the release of glucose from stored glycogen. It is also involved in generating glucose from amino acids.6 As a result, B6 plays an important role in a variety of health systems, from cognitive development to immune function.7 It is known to help the body produce antibodies; maintain healthy, normal nerve function; transport oxygen in red blood cells to tissues; break down proteins and regulate blood sugar levels.
Because B6 is water soluble, it cannot be stored in the body and must be consumed regularly in the diet. Food sources of vitamin B6 are plentiful such as: lean meats including beef, pork, and poultry; nuts, whole grains and fortified cereals; and produce including avocado, banana, legumes, and corn. However, processing, cooking and long-term storage of certain foods can reduce their pyridoxine content.8 Given that most American’s have a less than optimal diet of fresh and unprocessed foods, this may be one factor contributing to the rising rates of B6 deficiency.
Though severe B6 deficiencies remain relatively rare, growing numbers of people are either mildly deficient or at risk of deficiency. This can be prevalent among all age groups. Children, women and some adults are especially susceptible to low B6 levels. It is important to monitor this nutrients since the effects of a deficiency increase as it progresses.9 Symptoms may include weakness of the muscles, damage to nerves, and short-term memory loss.10
The impact of low B6
With more than 10 percent of the American population registering low B6 levels, there is a growing interest among researchers in how this vitamin might be implicated in current, prevalent health issues, including inflammation, depression and heart disease, to name a few. It is well known that vitamin B6 is important for the normal function of the immune system, with both animal and human studies suggesting that B6 deficiency can impact hormonal and cell-mediated immune response and may even have an influence on tumor growth and disease processes.11
More recently is the emergence of research on B6 and inflammation. In 2014, researchers in Norway began exploring how inflammation in the body may have an impact on vitamin B6 levels. By evaluating ratios of pyridoxal (PL) and pyridoxic acid (PA) to PLP as markers of vitamin B6 catabolism, they concluded that “broad specificity enzyme upregulated to reduce oxidative and aldehyde stress could explain increased catabolism of vitamin B6 during inflammation. The ratio PA: (PL +PLP) may provide novel insights into pathologic processes and potentially predict risk of future disease.
Cardiovascular health is another area where B vitamins play a key role, with vitamin B6, B12 and folic acid now known to help reduce homocysteine levels and potentially play a part in decreasing risk of stroke.12 However, few studies have looked at the effects of vitamin B6 alone on reducing risk of cardiovascular events and those that have failed to demonstrate a conclusive effect.13
Vitamin B6 in mental health and depression
Nutritional status is also critical for optimal mental health. Scientists are beginning to link B vitamins, especially B6 and B12, to the prevalence of depressive symptoms and the development of psychiatric disorders. In a 2016 study published in the journal Current Medicinal Chemistry, researchers noted the importance of B vitamins in general for functioning of the methylation cycle, monoamine oxidase production, DNA synthesis and the repair and maintenance of phospholipids. They noted that vitamin deficiency, including that of B6, may influence memory function, cognitive impairment, and dementia and further note that B1, B3, B6, B9 and B12 are essential for neuronal neurochemical pathways in depression. The researchers concluded that B vitamins contribute to the complexity of depressive symptoms.14
Another recent study in Clinical Nutrition Research looking at nutritional factors affecting mental health noted that B vitamins are involved in energy metabolism and can affect mental health, especially among the elderly who may experience age-related declines in these nutrients. In particular, folate, vitamin B6 and vitamin B12 are involved in homocysteine metabolism. As such, low levels of the B vitamins and high levels of homocysteine were observed in subjects with depression and dementia, among other disorders. They concluded that with the increasing life span of the population, age-related mental disorders could be on the rise and recommend dietary and supplement interventions to support cognitive function.15
B6 may be particularly important for women’s mental health. Research on intake of folate and vitamins B6 and B12 found some evidence that women with higher intake of vitamin B6 from food saw decreased risk of depression, whereas men saw a lower risk with higher intake of B12 from food.16
Women and B6
In addition to mental health, B6 is shown to be especially important for women in their reproductive years. Research indicates an association between low periconceptual vitamin B6 status and increased risk of preterm birth and early pregnancy loss. Given these findings, some researchers now suggest B6 as crucial at conception and for supporting a healthy pregnancy. While more research is warranted, given that many pregnancies are unplanned, it is suggested that women in their reproductive years maintain adequate B6 status.17
B6 can also address Premenstrual Syndrome. Although the exact prevalence of PMS is not known,18 it is a condition characterized by the presence of both physical and psychological symptoms. A randomized clinical trial concluded that vitamin B6, when taken with calcium, may help control PMS symptoms. Researchers now suggest supplementation with this combination for women who suffer from PMS.19
Similarly, vitamin B6 may also be helpful for women who experience nausea and vomiting in pregnancy. Though the symptoms are normal and generally go away, some studies have shown that B6 may be helpful in treating the condition. The American Congress of Obstetrics and Gynecology now recommends treatment with 10-25 mg of vitamin B6, three to four times daily to treat nausea and vomiting.20
Women who have diabetes may also be at higher risk for vitamin B6 deficiency. A 2012 study published in the journal of Applied Physiology, Nutrition and Metabolism investigated vitamin B6 metabolism in diabetes and noted that patients with Type 1 diabetes had greater alkaline phosphatase (ALP) activity, which can induce alteration in vitamin B6 metabolism. The authors concluded that these patients may be at a greater risk of vitamin B6 deficiency and complication from diabetes.21
B vitamins and sports performance
Given that B vitamins are essential for energy production, the absorption and transport of iron, and blood cell production, it follows that another line of emerging research focuses on the role of these nutrients specifically in athletes and for sports performance. While more research is needed, two recent studies note the importance of nutrient balance for athletes, especially for those who follow energy-restricted diets or do not have a balanced diet. One study notes that athletes may be more susceptible to nutrient deficiencies and recommend supplementation of B vitamins, as well as vitamins D, C and E in athletes.22
This effect may be especially important for active seniors whose energy levels are associated with nutrient status, including that of B6. One study noted that elderly athletes typically have a higher nutritional status than the recommended daily allowance and that these active seniors should be encouraged to maintain a high vitamin and mineral status.23
Populations at risk of deficiency
There are also several populations at particular risk for B6 deficiency. According to data from 2003-2004 NHANES analysis, plasma PLP concentrations were low even in some populations taking supplements. Among users and nonusers, the levels tended to be lower in women than men, non-Hispanic blacks than non-Hispanic whites, current smokers and people who were underweight. Teenagers had some of the lowest B6 levels, followed by adults age 21-44. Based on these findings, the authors concluded that the current RDA might not guarantee adequate B6 status is these specific population groups.24
A number of other effects may also lead to vitamin B6 deficiency. For example, alcohol consumption can have an impact on B6 levels. Individuals who abuse alcohol often show signs of lowered plasma levels of PLP because alcohol is associated with the removal of PLP from its enzyme.25 A number of diseases and health issues can also cause B6 deficiency. These include kidney disease, chronic renal insufficiency and autoimmune disorders. In addition, B6 deficiency can be caused by malabsorption problems like celiac disease, Crohn’s disease and ulcerative colitis. Patients with certain genetic disorders, such as homocystinuria, may also be at higher risk of B6 deficiency. 26
Certain medications can prompt low B6 concentrations as well. Patients taking medications to treat tuberculosis may be at risk for vitamin B6 deficiency because these medications can interact and bind with B6 causing inactivation. This can result in B6 deficiency symptoms including nerve damage.27 Antiepileptic drugs can also lead to deficiency over time.28
Bioavailability and Safety
Though most multivitamins do contain some B6, scientists are now starting to surmise that the recommended daily intake may not be enough to ensure adequate B6 levels for some populations. 29 That said, vitamin B6 is widely considered bioavailable, safe and not significantly different from form to form. Though there is not much concern regarding its toxicity, B6 has been examined in various opinions and found in excess to potentially contribute to neuronal damage and sensory and motor effects.30
Given these recent findings, a good diet of fresh unprocessed foods and supplementation with a multivitamin containing B6 are clearly good strategies for most patients. When assessing patient strategies, clinicians would be well advised to take a closer look specifically at B6, especially for patients in certain population groups, such as women and young adults, as well as for those with high risk factors, such as alcohol dependence, poor renal function and autoimmune disorders.
- Second National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population 2012. Accessed online at http://www.cdc.gov/nutritionreport/pdf/ExeSummary_Web_032612.pdf
- NIH Office of Dietary Supplements Vitamin B6 Fact Sheet, accessed online at https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/
- McCormick D. Vitamin B6. In: Bowman B, Russell R, eds. Present Knowledge in Nutrition. 9th ed. Washington, DC: International Life Sciences Institute; 2006.
- Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.
- International Life Sciences Institute; 2006.
- Leklum JE. Vitamin B6 In: Shils M, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th Baltimore. Williams & Williams, 1999-413-422.
- Mackey A, Davis S, Gregory J. Vitamin B6 In: Shils M, Shike M, Ross A, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006. 452-461.
- Aguilar F et al. Opinion on pyridoxial 5’-[phosphate as a source of vitamin B6 added for nutritional purposes in food supplements. The EFSA Journal 2008;760;1-13.
- International Life Sciences Institute; 2006.
- Fundamentals of Human Nutrition, Vitamin B6. Wikibooks. Accessed on line at https://en.wikibooks.org/wiki/Fundamentals_of_Human_Nutrition/Vitamin_B6
- Rall LC, Meydani SN. Vitamin B6 and immune competence. Nutr Rev. 1993 Aug;51(8):217-225.
- Saposnik G et al. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke 2009;40:1365-72.
- NIH Dietary Supplement Fact Sheet Vitamin B6. Accessed online at https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/
- Mikkelsen K et al. The effects of vitamin B in depression. Curr Med Chem 2016 Sept. 20. Epub ahead of print. PMID: 27655070. Access online at https://www.ncbi.nlm.nih.gov/pubmed/27655070
- Lim SY et al. Nutritional Factors Affecting Mental Health. Clin Nutr Res. 2016 Jul;5(3):143-52. Doi:10.7762/cnr.2016.5.3. Epub 2016 Jul 26.
- Gougeon L et al. Intakes of folate, vitamin B6 and B12 and risk of depressioin in community dwelling older adults: the Quebec Longitudinal Study on Nutrition and Aging. Eur J Clin Nutr. 2016 Mar;70(3): 380-5. Doi: 10.1038/ejcn.2015.202. Epub 2015 Dec 9.
- Ho CL et al. Prevalence and predictors of Low Vitamin B6 status in Healthy Young Women in Metro Vancouver. Nutrients Sep1;8(9). Pii:E538. Doi:10.3390/nu8090538.
- Braverman PK. Premenstrual syndrome and premenstrual dysphoric disorder. J Pediatr Adolesc. 2007;(1):3-12.
- Masoumi SZ, et al. Effect of Combined us of Calcium and Vitamin B6 on premenstrual Syndrome Symptoms: A randomized clinical trial. J Caring Sci 2016 mar 1;5(1):67-73. Doi: 10.15171/jcs/2016.007.
- ACOG (American College of Obstetrics and Gynecology) Practice Bulletin; nausea and vomiting of pregnancy. Obstet Gynecol. 2004;103:803-14.
- Massé PG et al. Type 1 diabetes impairs vitamin B6 metabolism at an early state of women’s adulthood. Appl Physiol Nutr metab. 2012 Feb;37(1):167-75.
- Eskici G. The importance of vitamins for soccer players. Int J Vitam Nutr Res 2016 May 10;1-21. Epub ahead of print. Doi: 10.1024/0300-9831/a000245.
- Chatard JC et al. Nutritional Status and physical fitness of elderly sportsmen. Eur J Appl Physiol Occup Physiol. 1998’77(1-2)”157-63.
- Fundamentals of Human Nutrition/Vitamin B6. WikiBooks.
- Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5′-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr 2008;87:1446-54.
- Dietary Supplement Fact Sheer Vitamin B6.
- Fundamentals of Human Nutrition/Vitamin B6. WikiBooks.
- Dietary Supplement Fact Sheet Vitamin B6.
- Am J Clin Nutrition 2008
- The EFSA Journal 2008