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TNFα theory for the beneficial effects of acupuncture on infantile colic: formula-fed infants and probiotic treatments
  1. Yusuf Ozgur Cakmak
  1. Correspondence to Yusuf Ozgur Cakmak, Department of Anatomy, Yeditepe University Medical School TR 34725 Istanbul, Turkey; cozgur{at}

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In an earlier article,1 I proposed a theory and described the supporting evidence for the pathways for the possible influence of tumour necrosis factor α (TNFα) on maternal breast milk and its influence on the pathophysiology of infantile colic. I emphasised how the increased TNF levels of a breastfeeding mother affect TNF, melatonin and serotonin levels of a colicky baby, and examined evidence for the direct and indirect regulatory effects of acupuncture over TNFα, serotonin and melatonin levels, and thereby infantile colic.

In a commentary on my paper,2 Reinthal et al stated that ‘Even if TNFα does play a role, this does not explain why children who are formula-fed may suffer from colic.’ However, it has been demonstrated that, compared with human milk-fed infants at 2 weeks, formula-fed infants produced (statistically significantly) more TNFα.3 Moreover, if the formula contains long-chain polyunsaturates, the levels of TNFα were further increased.3 In addition, it has been shown that the symptoms of infants with severe colic were reduced when they were given a cow's milk-free formula, and amplified with a formula that included cow's milk whey protein.4 It is worth noting that cow's milk can raise TNFα levels.5 Furthermore, over a 3-week period, a standard modified cow's milk formula was compared in a double-blind study with a soya milk formula. The duration of colic symptoms was significantly reduced during the week on soya milk (p<0.01).6 The reduced symptoms in the soya formula group can be explained by the exclusion of cow's milk as a source of TNFα in accordance with the TNFα theory, but also by the effect of soya itself. Interestingly, it has also been shown that ingestion of soy may help prevent fluctuations in plasma TNFα.7

Additionally, Escherichia coli were found to be more abundant in colicky infants,8 and it has been shown that TNFα augments E coli growth in vitro and in vivo.9 Moreover, after the E coli colonisation in gut microflora was shown in infantile colic, probiotic treatment options appeared to change the gut microflora. For example, administration of the probiotic Lactobacillus reuteri at a dose of 108 colony-forming units per day in early breastfed infants improved the symptoms of infantile colic in a randomised, double-blind, placebo-controlled trial.10 More recently, it has also been shown that L reuteri suppress human TNF production.11

Therefore, if we consider the regulatory control of acupuncture over TNFα, serotonin and melatonin which I described,1 in addition to published about the relationship of TNFα, feeding formulae, probiotic treatments and infantile colic, it appears that this TNFα-based theory is the only theory proposed that can provide an explanation for both the maternal milk-based factors (including maternal diet, smoking, sleeping disorders, depression, aspirin intake), and formula-based factors in infantile colic pathophysiology, as well as providing a basis for both the treatment of infantile colic with probiotics and the beneficial effects of acupuncture on the symptoms.


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  • Competing interests None.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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