Pyridoxine, also known as vitamin B6, is a supplement that many people take, either by itself or in a multivitamin. It is available over the counter, no prescription required. Most of the patients taking B6 with whom I have spoken, however, have very little idea what B6 does, and other than a general recommendation they have been given at some point, are not very clear about whether they should take it at all.
It is true that B6 deficiency can lead to illness. It is also true that taking too much B6 can be dangerous. Here, I am going to briefly explain the basics of B6 and take apart the common issues PD patients may face with this vitamin.
B6 is classified as a coenzyme. Coenzymes are small molecules that assist enzymes in chemical reactions. There are thousands upon thousands of these reactions going on all the time in your body. B6 is involved in over 100 enzyme reactions with proteins, amino acids, carbohydrates, and lipids. B6 helps to maintain homocysteine levels in the blood; is a participant in immune function; and is involved the development of cognition through the formation of neurotransmitters – those chemicals like dopamine that allow one nerve to communicate with another. Deficiency of B6 is therefore associated with many different conditions such as anemia, dermatitis, cheilosis (scaling of lips, and cracks at the corners of the mouth), immune dysfunction, glossitis (swollen tongue), confusion, irritability, seizures, neuropathy, and depression. In short, it is important to have normal B6 levels.
We get B6 by eating a healthy diet. It is found in fruits, grains, fish, poultry, beef liver and other organ meats, potatoes, and some other starchy vegetables. Absorbing nutrients from foods is not always easy, however, and this leads some to think that they should supplement B6 and other vitamins to “make sure” they are getting enough. This should not be done blindly.
It is true that some vitamins and minerals are absorbed by a special process, which may take several steps in the body. A failure of any one of the multiple biochemical steps required may cause poor absorption of the vitamin, and thus a deficiency. This is the case with B12, for example, but it is not the case for B6. B6 is absorbed passively in the jejunum, a part of the small bowel. When a vitamin is absorbed passively, absorption is not an energy-requiring process, and when one has good health, there is usually no obstacle to B6 moving freely into the blood stream. It would therefore seem easy to maintain a normal level of B6 in the body.
However, a small percentage of people will have B6 deficiency for a variety of reasons, such as kidney disease; celiac disease, Crohn’s disease, ulcerative colitis, and other malabsorption syndromes; autoimmune disease such as rheumatoid arthritis; alcohol dependence; and exposure to certain medications such as antiepileptic drugs. There is some data, also, that PD patients who take large amounts of levodopa may have low B6 levels (1, 2). Most of that data comes from European case reports of patients receiving continuous carbidopa/levodopa infusion via the Duodopa pump (not to be confused with Duopa in the United States), but it is also known that PD patients taking high doses of oral carbidopa/levodopa have a higher prevalence of chronic, sensory, axonal polyneuropathy (3), in other words, nerve damage. It should be noted that some studies point to a deficiency of B12 in these patients, and apparently B6 was not always measured. There is mounting evidence for both. It is not entirely clear how a B6 deficiency is happening in these patients. One possible mechanism involves carbidopa, which is meant to block an enzyme in the body called dopamine decarboxylase, so that levodopa makes it to the brain. However, carbidopa also inhibits the action of B6. It may also be that absorption of B6 is somehow blocked by carbidopa/levodopa, or that downstream biochemical reactions deplete B6 and B12. According to the prescribing information of carbidopa/levodopa (Sinemet), B6 and carbidopa/levodopa may be given safely together (4). Though there is no formal guideline recommending testing, it has been suggested by some authors that it might be worthwhile to check one’s blood level, especially if one is taking moderate to high doses of levodopa, or suffering from any of the above-mentioned disease states (1). Anecdotally, in my clinic I have diagnosed multiple PD patients taking carbidopa/levodopa with B6 deficiencies, where no other clear cause is evident.
The good news is that measuring a B6 level is done with a simple blood test, and replacement may be given with over-the-counter tablets. However, as with any supplement or medication, care should be taken in replacing B6, and to be clear, I re-emphasize that I am not recommending anyone take a B6 supplement without knowing one’s own blood level first. Ideally, a qualified physician should interpret the test and tell you whether you need B6 supplementation, and if so, how much you should take. The United States Recommended Daily Allowance (USRDA) daily dose for men over 50 is 1.7mg, and for women of the same age 1.5mg (5). In most individuals, this amount is readily obtainable with consumption of a healthy diet. Higher doses are sometimes recommended for short periods, for specific conditions. You should know that many over the counter vitamin supplements carry amounts of B6 that are far higher than this, sometimes into or over the 500% or “megadose” range. The Food Intake Board of the Institute of Medicine has established that for men or women over 50, the tolerable daily upper intake level of B6 is 100 mg (6), a dose commonly found in grocery stores. B6 at this dose is 59 times higher than USRDA for women and 67 times higher than USRDA for men.
Overdosing B6 can be dangerous for several reasons. Merck Pharmaceuticals has stated that B6 in doses of 10 mg to 25 mg may actually reverse the effects of levodopa by increasing the rate of the enzyme activity that carbidopa is meant to inhibit (4). In other words, levodopa is depleted in the body before it can get to the brain, where it is needed to work against PD. There is no mention of the effect on the same enzyme when B6 is given at 100, 500, even 1000mg (all doses which are available in some health food, drug, and grocery stores), though one would suspect it is even more potent in driving down levodopa, and thus worsening the symptoms of PD. In addition, much like the case when B6 levels in the body are too low, excess B6 is well documented to cause neuropathy, or nerve damage, as well as a disfiguring skin condition ( 7, 8,9). The Weill Cornell Neuropathy Center evaluated all new neuropathy consultations from July 2014 until June 2015 and found that 7% had elevated B6 levels; whereas only 1.5% combined had either B6, or B12 deficiencies (10). Among the total group studied abnormal levels of nutritional factors were implicated in 24%. Likewise, the Peripheral Neuropathy Center at Columbia University evaluated patients over a 10 year period ending in 2012 (11). These were new referrals with an existing diagnosis of idiopathic neuropathy, meaning another physician, typically a neurologist, had not yet determined the cause of the neuropathy. Among these patients, B6 toxicity accounted for 2.5%; whereas B6 deficiency was 0.3%, and B12 deficiency 1.4%.
In summary, some PD patients may have a high or low B6 level, and either may be harmful. There is some concern that carbidopa/levodopa may indirectly drive B6 levels down. B6 supplements may contain doses that are far too strong for daily use, and toxicity has been linked to neuropathy, and possible negative impact on PD symptoms. If you have concerns about your B6 level, have a qualified doctor check your level and advise you about how and whether to take B6.
REFERENCES (online sources as of mid September, 2016)
1. Müller et al. Peripheral neuropathy in Parkinson’s disease: levodopa exposure and implications for duodenal delivery. Parkinsonism Relat Disord. 2013;19(5):501-7.
2. Urban et al. Subacute axonal neuropathy in Parkinson’s disease with cobalamin and vitamin B6 deficiency under duodopa therapy. Mov Disord. 2010;25(11):1748-52.
3. Uncini et al. Polyneuropathy associated with duodenal infusion of levodopa in Parkinson’s disease: features, pathogenesis and management. J Neurol Neurosurg Psychiatry. 2015;86(5):490-5.
4. https://www.merck.com/product/usa/pi_circulars/s/sinemet/sinemet_pi.pdf
5.https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/
7. Schaumburg et al. Sensory neuropathy from pyridoxine abuse: a new megavitamin syndrome. N Engl J Med. 1983;309(8):445-448.
8. Barak N, Huminer D, Stahl B. Vitamin B6 (Pyridoxine) — excessive dosage in food supplements and OTC medications. Harefuah 2004;143(12):887-90, 910, 909.
9. de Kruijk JR, Notermans NC. Sensory disturbances caused by multivitamin preparations. Ned Tijdschr Geneeskd. 2005;149(46):2541-2544.
10. Latov et al. Abnormal nutritional factors in patients evaluated at a neuropathy center. J Clin Neuromuscul Dis. 2016;17(4):212-214.
11. Farhad et al., Causes of Neuropathy In Patients Referred As “Idiopathic Neuropathy” Muscle Nerve 2016;53:856-861
