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Clinical Review Interactive case report

Treating nausea and vomiting during pregnancy: case progression

BMJ 2004; 328 doi: (Published 05 February 2004) Cite this as: BMJ 2004;328:337

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Vitamin B6 for nausea and vomiting in pregnancy

The authors have chosen to use an n of 1 trial of vitamin B6 treatment for pregnancy sickness because of an interest in complementary or herbal medicine. Unlike much of alternative medicine, which often lacks a detailed scientific background, nutritional medicine is based on fundamental evidence based medical research. In the 1960s it was discovered that pregnancy and oral contraceptives lowered zinc, raised copper levels and caused vitamin B6 deficiencies.1,2 Many women are currently deficient in these and other essential nutrients like magnesium.3

Pregnancy, cortisol, oestrogens and oral contraceptives can induce vitamin B6 deficiency by increasing the activity of the enzyme tryptophan oxygenase, which requires vitamin B6 as a co-factor. Functional deficiency of vitamin B6 can impair the decarboxylation of dopa to dopamine. Vitamin B6 (pyridoxine) is converted into the active form, pyridoxal 5 phosphate, by riboflavin (vitamin B2) and magnesium. Vitamin B6 is required for normal essential fatty acid (EFA) desaturation and elongation. Zinc and magnesium are also required for EFA desaturation and such co-factor deficiencies block omega-6 and omega-3 EFA pathways causing deficiencies even when intake of first stage linoleic acid and alpha linolenic acid would otherwise be adequate. Repletion of cofactors is important because attempting to use only omega-6 EFAs or only omega-3 EFAs as a pharmaceutical4 can cause deficiencies in the other pathway. Zinc is necessary for the transport of vitamin B6 across cell membranes into the cell. Deficiency impedes the absorption of zinc and may impair cellular immunity and diminish antibody responses. A woman with vitamin B6 deficiency will consequently have disturbed protein, fat and carbohydrate metabolism and immunity.4-6

Biolab functional blood tests find B vitamins are most the most commonly deficient vitamins. A majority of patients are vitamin B6 deficient (an individual test costs £15) but they are usually given supplements with a group B vitamin complex to prevent supplementation of one B vitamin causing a deficiency of another B vitamin. For example, repletion of vitamin B 6 deficiency will increase the demand for vitamin B2. Why therefore would an unscreened pregnant woman be expected to become asymptomatic when supplemented with only one essential nutrient for two days out of five? Primary dysmenorrhoea, pregnancy sickness, premenstrual syndrome, and menopausal flushing, are usually warning signs of multiple biochemical upsets and an inability to cope with changes in hormone levels. Common nutritional deficiencies increase adverse reactions to foods and chemicals.3 Therefore giving sporadic or continuous single nutrient supplementation, or even pharmaceutical drugs, is unlikely to prevent the recurrence of daily symptoms.

Pregnancy sickness should be taken seriously as a signal of nutrient deficiencies. It should not be regarded as an opportunity for randomised trials of pharmaceutical drugs or unmonitored single nutritional supplements. Pregnancy is about feeding a growing foetus with optimal quantities of nutrients. Preconceptional and maternal nutritional deficiencies are extremely common.6 Without evidence based advice on essential nutrient supplementation and the implementation of low allergy dieting, a pregnant woman suffering from nausea and vomiting is unlikely to be treated efficiently and she will not be able to achieve adequate blood levels of nutrients for her foetus. The effects may last for generations as has been indicated by animal studies.7

1. How does the evidence obtained from the n of 1 trial differ from the evidence of randomised controlled trials?

The n of 1 trial is an inappropriate way to treat symptoms of pregnancy sickness with a single essential nutrient supplement. If such symptoms were caused by a single nutrient deficiency, or if use of a single nutrient like vitamin B6 given in a relatively low dose, had pharmaceutical actions, continuous treatment would be more likely to show an effect in a standard randomised controlled trial.

2. How would you apply this evidence to other patients presenting with nausea and vomiting in pregnancy?

I would not apply this evidence to other patients as I do not expect this trial to give a meaningful result. Even if sporadic use of vitamin B6 helped this patient I would not assume all patients were vitamin B6 deficient.

3. Can you think of other clinical dilemmas that would be helped by the use of n of 1 trials?

N of 1 trials could be of use in individuals who were not pregnant and who were willing to test short acting pharmaceutical drugs. Examples would be testing the effects of antihistamines, anti-emetics or analgesics for hay fever, sea sickness or otherwise untreatable chronic pain, respectively. Parenteral nutrients could be beneficial in the short term for some patients, for example magnesium for eclampsia but, as nutritional deficiencies can be diagnosed accurately, failing to investigate and replete seems unethical. Diagnosable nutrients deficiencies are not suitable for either type of trial. There is a need for nutritional analyses to become more widely available.

1 Halsted HJ, Hackly BM, Smith JC. Plasma zinc and copper in pregnancy and after oral contraception. Lancet 1968:2:278-83.

2 Rose DP. The effects of gonadol hormones and oral contraceptives on tryptophan metabolism. In: Eds Salhanick HA, Kipnis DM, Vande Weile RL. Metabolic effects of gonadal hormones and contraceptive steroids. London-- New York: Plenum Press, 1969 pp352-65.

3 Grant ECG. The pill, hormone replacement therapy, vascular and mood over-reactivity, and mineral imbalance. J Nutr Environ Med 1998;8:105-116.

4 Anthony H, Birtwhistle S, Eaton K, Maberly J. Environmental Medicine in Clinical Practice. BSAENM Publications 1997, pp173-4.

5 Grant ECG. The influence of hormones on headache and mood in women. Hemicrania 1975;6:2-10.

6 Horrobin DF. Gamma linolenic acid: an intermediate in essential fatty acid metabolism with potential as an ethical pharmaceutical and as a food. Rev Contemp Pharmacother 1990:1:1-45.

6 Barnes B, Grant ECG et al. Nutrition and preconception care. Lancet 1985;2:1297.

7 Passwater RA, Cranton EM. In: Trace elements, hair analysis and nutrition. Keats, New Canaan, Connecticut: 1983:291-303.

Competing interests: None declared

Competing interests: No competing interests

08 February 2004
Ellen C G Grant
Physician and medical gynaecologist
20 Coombe Ridings, Kingston-upon-Thames, Surrey, KT2 7JU, UK