by Jeffrey Dach, MD
Jim is a 46 year old retired New York policeman who uses power tools to repair his house. His problem is chronic pain at the base of the thumb and wrist. The pain worsens with use of the hand, making it difficult to use the power tools. Other repetitive motions cause pain such as turning a key in a lock, unscrewing the lid of a jar, and opening the car door. Jim also has “trigger finger” involving the thumb joint, and at night, before sleep he notices tingling and numbness in the hands.
Left image wrist / hand anatomy courtesy of wikimedia commons.
Conventional Treatment – Steroid Injection and Splint
Jim’s hand pain worsened lately, so he went to a hand surgeon who gave him a steroid injection at the base of the thumb and applied a hand/wrist splint. These measures were ineffective, and his pain continued. The surgeon offered an operation. Jim came into the office to ask if anything else could be done to avoid surgery. I first learned of B6 for carpal tunnel from reading Dr Jonathan Wright’s newsletters. Credit and thanks goes to Dr. Jonathan Wright.
Left image wrist splint courtesy of wikimedia commons.
P-5-P, Vitamin B6, Pyridoxine for Trigger Finger
As it turns out, there is a simple and effective vitamin therapy for Jim’s Trigger Finger hand condition called Pyridoxine, vitamin B6. Jim was given a bottle of pyridoxine phosphate (the activated form) and 3 weeks later, an amazed Jim returned to report that his pain and swelling is gone, and his trigger finger had also resolved. He no longer needs the operation. Left image diagram of Vitamin B6 courtesy of wikimedia commons.
Magnesium Added to Improve Effect
The addition of a magnesium supplement has been noted to improve the effectiveness of B6 for neurological and musculo-skeletal conditions.
“The Doctor Who Looked At Hands”, the Book by John Ellis MD
Old copies of “The doctor who looked at hands”,by John Ellis MD originally written in 1966, are still available.
Dr. John Ellis was a Texas physician practicing in the 1960’s. He discovered that vitamin B6 eliminates carpal tunnel syndrome, trigger finger, and other hand conditions.
Examine the backs of your hands. Have you ever noticed the backs of your hands are puffy and swollen, making the tendons obscured? Are your hands so swollen that you cant touch your palms with the tips of your fingers? That’s the positive “Ellis sign,” indicating extra B6 could be helpful. Usual dosage is 20 milligrams three times daily of the activated P-5-P form of B6.
Thickening of the Flexor Tendon Sheath Treated with B6
Stenosing teno-synovitis, a thickening of the flexor tendon sheaths, is quite common in carpal tunnel syndrome, as well as trigger finger syndrome.(1-3) The B6 vitamin, the P-5-P form of Pyridoxine is a useful treatment for carpal tunnel, trigger finger and the associated tendon sheath thickening.(1-4)(link)(link)(link)
Vitamin B6 Toxicity, Monitoring Blood Levels and Dosage
Unlike other water soluble B vitamins which are safe even at high doses, vitamin B6 (pyridoxine) can be toxic at dosages above 300 mg per day causing sensory neuropathy. Having no reported toxicity is the pyridoxal-5-phosphate (P-5-P) form of B6 which is also the biologically active form of the vitamin. Therefore, P-5-P is the preferred form of the vitamin B6 to take. Make sure your B Vitamin Complex uses the P-5-P version rather than plain old pyridoxine version. We routinely measure serum P-5-P levels just to be on the safe side.
In a 2009 study in AJCN, P-5-P levels were measured, and the authors recommended the following B6 protocol: Most of the patients required 25–50 mg B6 daily.
For Serum P-5-P concentration GREATER THAN 3.3 ng/mL – No treatment
For 2.5–3.2 ng/mL – 50 mg pyridoxine HCl/d
For LESS THAN 2.5 ng/mL – daily oral dose of 50 mg
Normal reference range: 3.3–26 ng/mL. Dose reduction or discontinuation of maintenance therapy was based on serum concentrations 25 and 50 ng/mL, respectively.
Plasma PLP below 30 nmol/L has been used as an indicator of inadequate status while a cutoff of 20 nmol/L indicates deficient concentrations. Both cutoffs have been widely used in the literature and demonstrate utility in assessing adequacy of vitamin B6 intake.
Jeffrey Dach MD
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Davie Fl 33314
954 792 4663
Links and References:
J Hand Surg Br. 1987 Jun;12(2):229-32.
Pathology of the flexor tendon sheath in the spontaneous carpal tunnel syndrome.
Neal NC, McManners J, Stirling GA.
The histological features of the flexor tendon sheath in the spontaneous carpal tunnel syndrome were studied. The main differences between our findings and previous studies were twofold. Firstly a striking absence of inflammation in our material and secondly the diversity of the pathological changes encountered–alterations in the connective tissue especially the collagen; proliferation with thickening of the tissues of the tendon sheath; fibrosis; amyloid deposition; oedema; vascular lesions including thickening of vessels walls, intimal hyperplasia, and thrombosis; and a foreign body giant cell reaction. Although the lesions described here may not be significant in every case in which they are encountered, they do appear to support the view that pressure in the carpal tunnel and ischaemia are the important factors in a majority of cases of the spontaneous carpal tunnel syndrome.
Response of vitamin B-6 deficiency and the carpal tunnel syndrome
to pyridoxine . Proc. NatL Acad. Sci. USA Vol. 79, pp. 7494-7498, December 1982 Medical Sciences, (neuropathy/nutrition/vitamin supplementation/diet) JOHN M. ELLIS*, KARL FOLKERSt, MOISE LEVYt, SATOSHI SHIZUKUISHIt, JAN LEWANDOWSKI§,
SATOSHI NISHIIt, H. A. SCHUBERTf, AND RICHARD ULRICH
Folkers and co-workers (1, 2) initiated a study to detect and quantitate human deficiencies of vitamin B-6 by the determination of the specific activities and percentage deficiencies of the glutamic oxaloacetic transaminase of erythrocytes (EGOT). Ellis et al. (3) reported that a deficiency of vitamin B-6 existed in patients who had the carpal tunnel syndrome (CTS). Ellis et
al. extended the EGOT data to show a severe deficiency of vitamin B-6 in 10 patients (4) and 11 more patients (5). Comprehensive biochemical (6) and clinical studies (7), including crossover
treatment, with pyridoxine and placebo were conducted on the exemplary 22nd patient with CTS. For all patients receiving therapy with pyridoxine, the B-6 deficiency was corrected and the neurological syndrome was alleviated. Becker and Granger (8) described CTS as a “common clinical entity,” often associated with rheumatoid arthritis, obesity, myxedema, diabetes, pregnancy, and other conditions. “Rheumatic” conditions associated with this syndrome have included “tennis elbow,” Dupuytren contracture, deQuervain disease, “trigger fingers,” bursitis, and periarthritis of the shoulder. From data on 1,215 patients with CTS at the Mayo Clinic between 1930 and 1960, Yamaguchi et al. (9) made the astounding observation that some patients had had the symptoms for up to 40 years.
The most common clinical findings were paresthesias, thenar muscle weakness and atrophy (which we now believe may result from many years of a severe deficiency of vitamin B-6), and positive Phalen and Tinel signs. When the compression of the median nerve in the carpal tunnel exists for many years, there may be a permanent sensory and motor loss. The synovium is involved, and the symptoms appear to result from tenosynovitis. Phalen (10) and Maxwell et al. (11) reviewed diseases associated with CTS. Tobin (12) and Sabour and Fadel (13) observed the syndrome in connection with pregnancy and use of the “pill. ” Morelli and Sala (14) stated “the treatment . . . clearly must be surgical.” Dolenc and Trontelj (15) asserted “microsurgery is a method ofchoice in the treatment of pressure neuropathies. ” Treatment by local injection or systemic administration ofcorticosteroids has been used.
Surgery has been widely practiced, providing relief (16), often erratically, of limited duration, and no relief for up to 20% of those so treated. For our 23rd to 29th patients, the EGOT data revealed a severe deficiency of vitamin B-6, and they were treated, in double- blind fashion, with pyridoxine and a placebo. Patients on placebo were treated with pyridoxine on a cross-over basis. The double-blind assessment was successful. The results are described
Klin Wochenschr. 1989 Jan 4;67(1):38-41.
Carpal tunnel syndrome and vitamin B6. Laso Guzmán FJ, González-Buitrago JM, de Arriba F, Mateos F, Moyano JC, López-Alburquerque T. Departamento de Medicina, Hospital Clinico Universitario, Salamanca, Spain.
Twelve patients with carpal tunnel syndrome were studied. Clinical and electrophysiological data were obtained and an estimation of vitamin B6 (pyridoxine) status by an assay of erythrocyte aspartate aminotransferase and coenzyme stimulation assay were done. None of the patients was found to have vitamin B6 deficiency. Patients were treated with 150 mg of pyridoxine daily for 3 months. Erythrocyte aspartate aminotransferase increased significantly (p less than 0.001) in all the patients. In 6 patients there were clinical and electrophysiological improvement and erythrocyte aspartate aminotransferase increased more than in the other 6 patients. The data obtained appear to indicate that although vitamin B6 deficiency is not common in carpal tunnel syndrome patients, pyridoxine supplementation can be recommended as adjuvant treatment in those patients undergoing surgery.
Res Commun Chem Pathol Pharmacol. 1977 Jun;17(2):283-93.
Deficiency of vitamin B6 in women taking contraceptive formulations.
Kishi H, Kishi T, Williams RH, Watanabe T, Folkers K, Stahl ML.
The specific activities (S.A.) of the glutamic oxaloacetic transaminase from erythrocytes (EGOT) of 75 women taking 16 diversified contraceptive formulations were determined by the principle (CAS) of unsaturation and saturation of receptors of the Coenzyme-Apoenzyme-System with the coenzyme, pyridoxal 5′-phosphate. 52 women were not taking pyridoxine; 20 were taking 1-5 mg; 3 were taking 25-100 mg. The mean basal S.A. of the 52 women without pyridoxine was lower (p less than 0.01) than for the 20 on 1-5 mg. The mean basal S.A. for the women on 25-100 mg was higher (p less than 0.01) than for the women without pyridoxine. The mean % deficiency for the women on 25-100 mg was negligible and lower (p less than 0.01) than 18+/-8 for the 52 women, and 14+/-6 for the 20 women. These data indicate that 1-5 mg of pyridoxine is inadequate for women on contraceptives. The requisite daily dosage is projected at 50-100 mg. Other data indicate that 5-12 weeks of supplementation with pyridoxine can be required to reach a stable “ceiling” of S.A. of EGOT. This period indicates some regulatory mechanism by diminished levels of the apoenzyme upon gene expression to bring about normal levels of the transaminase.
J Nutr Sci Vitaminol (Tokyo). 1981;27(3):193-7.
Distribution of vitamin B6 deficiency in university students. Shizukuishi S, Nishii S, Folkers K.
The basal specific activities (S.A.; mumol of pyruvate/hr/10(8) erythrocytes) and the % deficiencies of activity of the glutamic oxaloacetic transaminase of the erythrocytes (EGOT) of 174 university students was 0.28 +/- 0.05 and 33 +/- 9%, respectively. There was a negative correlation, r = -0.65 (p less than 0.001), between the mean basal S.A. and the mean % def. (i.e., the lower the S.A., the higher the % def.). There were students with low basal S.A.’s who showed symptoms of carpal tunnel syndrome. On the basis of these data, 93% of 174 students had deficiencies of 20% and higher which was potentially correctable by oral pyridoxine; these students had B6-deficient diets. On the basis that a normal basal S.A. may be 0.7, and that the maximum S. A. (0.45) for all 174 students is about 65% of 0.7, all 174 students had varying vitamin B6 deficiency, and their diets provided inadequate amounts of this vitamin.
Plast Reconstr Surg. 1987 Mar;79(3):456-62.
Carpal tunnel syndrome and vitamin B6.
Kasdan ML, Janes C. We reviewed 1075 patients presenting over a 12-year period with symptoms of carpal tunnel syndrome. A total of 994 had a final diagnosis of carpal tunnel syndrome. There were 444 male and 550 female patients with a mean age of 42 years. Three-hundred and ninety-five related symptoms to their job. Surgery was performed in 27 percent of the total diagnosed cases with approximately 97 percent relief of symptoms. Satisfactory alleviation of symptoms was obtained in 14.3 percent of patients treated conservatively prior to 1980, with one or a combination of splinting anti-inflammatory agents, job or activity change, and steroid injections. In 1980, vitamin B6 (pyridoxine) was added as a method of conservative treatment. Satisfactory improvement was obtained in 68 percent of 494 patients treated with a controlled dosage (100 mg b.i.d.). While our findings were not the result of a controlled scientific study, we feel they suggest that regulated use of vitamin B6 may be helpful in treating many cases of carpal tunnel syndrome.
Ann Plast Surg. 2001 Aug;47(2):153-60.
Experimental model of pyridoxine (B6) deficiency-induced neuropathy.
Dellon AL, Dellon ES, Tassler PL, Ellefson RD, Hendrickson M. Division of Plastic Surgery and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
A pyridoxine (B6) dietary deficiency was studied in female adult Sprague-Dawley rats by hind-limb walking-track analysis. Serum levels of pyridoxine and three metabolites were quantified by high-pressure liquid chromatography with fluorescence measurement. Morphometric analysis of the sciatic and posterior tibial nerves (from within the tarsal tunnel) was performed after 1 year on a diet deficient in vitamin B6. The B6-deficient rats developed abnormal walking-track patterns by 8 months, and these track parameters were different from age- and sex-matched normal diet control rats at the p < 0.05 level. Adding B6 at 10 parts per million to the diet then partially corrected these parameters, whereas the addition of 30 parts per million B6 corrected the abnormal pattern completely. Serum pyridoxal concentration correlated with the functional parameters, dropping from a mean of 115 mg per liter to 39.5 mg per liter (p < 0.05), and correcting with the B6 additive. Morphometric analysis demonstrated that the B6-deficient nerve from the tarsal tunnel had a decreased nerve fiber density (p < 0.001), with a normal total myelinated nerve fiber number, and an increased axon-to-myelin ratio (p < 0.003). It is concluded that a diet totally deficient in vitamin B6 results in a peripheral neuropathy.
Pyridoxine Pyridoxal 5’Phosphate. Alternative Medicine Review x Volume 6, Number 1 x 2001.Pyridoxine Pyridoxal 5 Phosphate Alternative Medicine Review Volume 6 Number 1 2001
J Am Coll Nutr. 2008 June; 27(3): 421–427. PMCID: PMC2572855
Vitamin B6 Is Associated with Depressive Symptomatology in Massachusetts Elders
Cristina Merete, MS, Luis M. Falcon, PhD, and Katherine L. Tucker, PhD
Vitamin B6 is needed for normal function of nerve cells and is the most frequently used and well-known nutritional treatment for CTS. It has been reported that people with CTS are frequently deficient in vitamin B6, and yet other doctors have not found a link. At very high levels vitamin B6 can damage sensory nerves, leading to numbness in the hands and feet as well as difficulty in walking. It is believed that vitamin B6 is usually safe in amounts of 200-500mg per day.
John Marion Ellis, M.D., together with well-known and respected medical researchers, was able to conclusively demonstrate that the synovium surrounding tendons underwent changes in the absence of vitamin B6, that resulted in Carpal Tunnel Syndrome, Tendonitis and Tenosynovitis, as well as many other forms of soft-tissue diseases. Two African Americans, Leo Strong and Eugene Howard, “over a period of 11 months gave 79 test tubes of blood during research that associated crippling disease with human vitamin B6 deficiency. Laboratory data on Strong was published in Proceedings of National Academy of Sciences, 1978, and clinical data in American Journal of Clinical Nutrition, 1979. “In a successful double blind study (where neither the doctor or patient know who receives the B6 and who receives the placebo), Howard, 1980, by videotape demonstrated improvement of crippling in hands and shoulders following treatment with vitamin B6. Results were conclusive.”1
Dr. Ellis wrote, “I firmly believe that 90% of what is called arthritis in the United States is, in reality, a biochemical change in synovium of tendons and joints, particularly in the fingers, thumbs, elbows, shoulders, knees and hips. With these changes in synovium, a person experiences swelling, pain and stiffness of the joints, symptoms that most men and women as well as doctors call ‘arthritis.’ . . . as Karl Folkers [Ph.D., then Ashbel Smith Professor and director of the institute for Biomedical research, University of Texas, Austin, TX] and I have proved, these conditions respond favorably to adequate amounts of pyridoxine, given over a period of 90 days. Many of my patients experienced relief in only a matter of weeks, but in the majority of cases, it does take about six weeks for the symptoms to start disappearing, and twelve weeks for a definitive response. In cases of severe stiffness, there will be gradual improvement up to a year.”1 Dr. Ellis recommends 25-300 mg of B6 a day depending on the person’s biochemistry. The following are just two cases of Dr. Ellis with positive results:
Joseph DeChamp had severe stiffness in all fingers of both hands, with 40% loss of flexion and extension. After receiving vitamin B6, 200-500 milligrams daily for 12 weeks the severe stiffness subsided remarkably in the fingers and the Carpal Tunnel Syndrome disappeared.1
Sarah Black had extreme swelling of hands and feet accompanying pregnancy as well as Carpal Tunnel Syndrome. Both of these conditions responded spectacularly to vitamin B6. Sarah’s husband, Gerald, also sought help from Dr. Ellis for Carpal Tunnel Syndrome. After twelve weeks of treatment with 100 mg of vitamin B6 daily, all swelling, numbness, tingling, and severe stiffness of fingers subsided in both hands.1
Vitamin B6 Therapy The Case of Tunis Johnson
Tunis Johnson, a fifty-five year old cook with Carpal Tunnel Syndrome, arteriosclerosis and diabetes mellitus, stated that he could not feel the weave in a tablecloth with his fingers. He was treated by John Ellis, M.D., with vitamin B6, 50 milligrams daily, had a remission of the problem until he went off of the vitamin for seven weeks because of an operation. When Dr. Ellis placed Tunis back on the vitamin, the Carpal Tunnel Syndrome again disappeared.4
The Case of Ellen Cardwell
Ellen Cardwell had unsuccessful surgery for Carpal Tunnel Syndrome. After taking vitamin B6 numbness, tingling, swelling and severe stiffness was relieved.4
The Case of Joseph DeChamp
Joseph DeChamp had severe stiffness in all fingers of both hands, with 40% loss of flexion and extension. After receiving vitamin B6, 200-500 milligrams daily for 12 weeks the severe stiffness subsided remarkably in the fingers and the Carpal Tunnel Syndrome disappeared.4
The Cases of Sarah and Gerald Black
Sarah Black had extreme swelling of hands and feet accompanying pregnancy as well as Carpal Tunnel Syndrome. Both of these conditions responded spectacularly to vitamin B6. Sarah’s husband, Gerald, also sought help from Dr. Ellis for Carpal Tunnel Syndrome. After twelve weeks of treatment with 100 mg of vitamin B6 daily, all swelling, numbness, tingling, and severe stiffness of fingers subsided in both hands.4
The Research of John Marion Ellis, M.D.
John Marion Ellis, M.D., together with well-known and respected medical researchers, was able to conclusively demonstrate that the synovium surrounding tendons underwent changes in the absence of vitamin B6, that resulted in Carpal Tunnel Syndrome, Tendinitis and Tenosynovitis, as well as many other forms of soft-tissue diseases. [See Osteoarthritis: Little Known Treatments and Bursitis (Fibromyalgia; Fibromyositis; Fibrositis; Rheumatism) this Foundation.]
Two African Americans, Leo Strong and Eugene Howard, “over a period of 11 months gave 79 test tubes of blood during research that associated crippling disease with human vitamin B6 deficiency. Laboratory data on Strong was published in Proceedings of National Academy of Sciences, 1978, and clinical data in American Journal of Clinical Nutrition, 1979.
“In a successful double blind study (where neither the doctor or patient know who receives the B6 and who receives the placebo), Howard, 1980, by videotape demonstrated improvement of crippling in hands and shoulders following treatment with vitamin B6. Results were conclusive.”4
Dr. Ellis wrote, “I firmly believe that 90% of what is called arthritis in the United States is, in reality, a biochemical change in synovium of tendons and joints, particularly in the fingers, thumbs, elbows, shoulders, knees and hips. With these changes in synovium, a person experiences swelling, pain and stiffness of the joints, symptoms that most men and women as well as doctors call ‘arthritis.’ . . . as Karl Folkers [Ph.D., then Ashbel Smith Professor and director of the institute for Biomedical research, University of Texas, Austin, TX] and I have proved, these conditions respond favorably to adequate amounts of pyridoxine, given over a period of 90 days. Many of my patients experienced relief in only a matter of weeks, but in the majority of cases, it does take about six weeks for the symptoms to start disappearing, and twelve weeks for a definitive response. In cases of severe stiffness, there will be gradual improvement up to a year.”4
Aspirin or some other form of non-steroidal anti-inflammatory drug (NSAID) is often used to inhibit pain during the 90 days or so of treatment, according to Dr. Ellis.4
“People with Carpal Tunnel Syndrome often have a large deficiency of vitamin B6, or have lifestyle factors that inhibit B6 metabolism such as stress, or ingesting Yellow Dye No. 5, and tartrazine derivatives. “. . . a deficiency in vitamin B6 (pyridoxine) may cause a pyridoxine-responsive neuropathy (nerve disorder).”3
Dosages of B6 range from 25-300 mg per day, depending upon a person’s biochemistry.
Pyridoxine (B6) is a group of related compounds: pyridoxine, pyridoxal, and pyridoxamine.1 An overdosage of pyridoxine may create nerve disorders in doses as low as 300 mg daily, if taken for long periods. However, most cases of toxicity have been reported when the dosages range between 2 and 5 grams per day, rather than milligram quantities.3 To avoid the possibility of such toxicity, many physicians prefer to supplement with pyridoxal-5-phosphate, a metabolite of pyridoxine.
The “pyridoxal-5- phosphate,” or P5P, form of vitamin B6 works the best.
Ever heard of Dr. John Ellis? He’s the Texas physician who discovered that vitamin B6 can eliminate carpal tunnel syndrome, trigger finger, and other hand conditions.
Look at the backs of your hands. Have you noticed that they’re a bit puffy and swollen and that you can’t see the tendons? Try holding your hands upright, keeping the joints joining your palms and fingers perfectly straight. Now try and bending the middle and end joints so that your fingertips touch your palms. Can’t do it? That’s a positive “Ellis sign,” and it means you need extra vitamin B6. Try 100 milligrams three times daily for up to six months—until all the puffiness is gone, you can see your tendons, the “Ellis sign” is gone, and your hands are much more flexible. If you’re interested, you can try to find an old copy of Dr. Ellis’ book The Doctor Who Looked at Hands at the library or on the Internet.
Ann Rheum Dis. 2006 December; 65(12): 1666–1667.
Pyridoxine toxicity courtesy of your local health food store by C D Silva and D P D’Cruz
Med J Aust. 1987 Jun 15;146(12):640-2.
Pyridoxine neuropathy. Waterston JA, Gilligan BS. A case of sensory neuropathy in a young woman due to long-term ingestion of pyridoxine, with subsequent recovery, is described. Pyridoxine neuropathy may occur after the long-term ingestion of doses as low as 200 mg a day. Because of its widespread use in the community, both the general public and the medical community need to be aware of this recently described complication of megavitamin therapy.
Neurology. 1985 Oct;35(10):1466-8. Sensory neuropathy with low-dose pyridoxine.Parry GJ, Bredesen DE. We describe 16 patients with neuropathy associated with pyridoxine abuse. The clinical picture of a pure sensory central-peripheral distal axonopathy was consistent. Pyridoxine dose was 0.2 to 5 g/d, and duration of consumption before symptoms was inversely proportional to the daily intake. In all patients with adequate follow-up, improvement followed discontinuation of pyridoxine. The ready availability of up to 1-gram tablets makes it likely that this neuropathy will continue to be seen.
N Engl J Med. 1983 Aug 25;309(8):445-8.
Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome.
Schaumburg H, Kaplan J, Windebank A, Vick N, Rasmus S, Pleasure D, Brown MJ.
We describe seven adults who had ataxia and severe sensory-nervous-system dysfunction after daily high-level pyridoxine (vitamin B6) consumption. Four were severely disabled; all improved after withdrawal. Weakness was not a feature of this condition, and the central nervous system was clinically spared. Although consumption of large doses of pyridoxine has gained wide public acceptance, this report indicates that it can cause sensory neuropathy or neuronopathy syndromes and that safe guidelines should be established for the use of this widely abused vitamin.
Indices of Pyridoxine Levels on Symptoms Associated with Toxicity: A Retrospective Study
Aliya N. Chaudary;1 Adam Porter-Blake;2 Patrick Holford2 Conclusions: There appeared to be no association between symptoms associated with vitamin B6 toxicity and vitamin B6 dose (between 30mg and 230mg) during a period of 3–27 months. A suitable vitamin B6 NOAEL of 100 mg / day and a suitable LOAEL of 150 mg / day is suggested.
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