4.1. Benefits of a Nutrient-Rich Diet
This non-randomized controlled study showed a decline in clinical complaints of fatigue in children following the advised diet, especially in the need to rest and sleep. Patients took fewer naps and spent less time in bed during the day when following the advised diet. The observed positive effect on fatigue can be explained by an increased intake of minerals, vitamins and fatty acids [18
]. Four further factors can explain these results, including a beneficial effect of combining nutrients, effects of anti-oxidants, better sleep behavior due to the high concentration of melatonin in milk [30
], and an improvement of the immune function.
Vitamins and minerals have been shown to mutually benefit their absorption when consumed simultaneously. The intake of green vegetables appeared to have the strongest impact on fatigue, especially for cognitive fatigue. This could be because vitamins A and C in green vegetables improve the absorption of other minerals such as zinc [31
], magnesium [33
] and iron [34
]. Vitamin A can even reduce iron-dependent anemia [34
]. Previous studies focused on individual nutritional supplements rather than on diets, which do not fully take into account this mutually beneficial effect. On top of this, it has been shown that pure nutrients are absorbed better than artificial nutrients [33
]. For example, a study with an artificial polynutrient supplement (multivitamin pill) did not result in a significant difference in the feeling of fatigue [36
]. A stronger impact on fatigue could therefore be explained by the pure nutrients in the advised diet versus
Beside vitamins and minerals, green vegetables and melatonin in whole milk contain many anti-oxidants, which can reduce oxidative stress in the human body [30
], which is associated with fatigue in children [16
]. A reduction of oxidative stress by an increased consumption of green vegetables and whole milk could partly explain the decrease in fatigue.
Melatonin has more beneficial properties on fatigue, especially on sleep behavior. Whole milk is known to contain high melatonin levels [40
], which has been shown to be effective in improving sleep onset, maintenance of sleep, and prolongation of sleep [30
]. Our study demonstrated that whole milk is significantly associated with a decreased need to sleep or rest, and that there was a stronger decline in fatigue in children who drank more whole milk than in children who drank less whole milk. As most children did not drink whole milk before the start of the diet, an increased supply of melatonin may have improved their sleeping behavior and feeling of wellbeing as well.Surprisingly, the effect of drinking whole milk was not related to the time it was consumed, as the result was also found when it was consumed in the morning or afternoon. We hypothesize that an increased ingestion of melatonin stimulates the body’s own production of melatonin at night.
Additionally, the components of the advised diet can improve the immune function in children. Earlier studies in our hospital showed that this diet has a beneficial effect on recurrent upper respiratory tract infections [6
]. This is supported in the literature by an improvement of the immune functions by vitamins and minerals, which are present in high concentrations in the advised diet [41
]. Even without recurrent infections, improvement of the immune system can be reflected in the general wellbeing, and an increase in energy due to less pro-inflammatory cytokines [43
Finally, no significant change in BMI was measured in our study. We evaluated the effect of the advised diet on the BMI as full fat dairy products are generally not advised for children [44
]. However, beneficial effects of full fat dairy products on asthma [45
] and metabolic syndrome in children have been observed before, without an increase in BMI [29
]. We therefore encourage the advised normal portions of full fat dairy products.
As the prevalence of fatigue in children is high, therapeutic options are limited, and there is little research on the impact of nutrition, this study is highly clinically relevant. We saw a clear clinical improvement in fatigue, which was also noticed by the children’s parents. Children seemed healthier and more resilient, and their parents observed less need to sleep or rest and more energy for daily activities. Moreover, the diet is an elegant, safe, low-cost, and easy treatment for fatigue and can be combined with therapy for other medical conditions.
4.2. Limitations and Future Perspectives
Although the results of this study are highly relevant, there are several limitations. Firstly, the study groups were small and not randomized because this was the first trial to investigate the effect between a nutrient rich diet and fatigue. Furthermore, the intervention was not performed in a double-blind fashion. Although the PedsQL is a validated method for objectifying fatigue [26
], it remains a subjective measure. The group of children studied consists of children who are simply fatigued and children with comorbidities and use of medication. The percentage of children with comorbidities and medication-usage was the same in both groups but could still influence the effect of the advised diet. A sensitivity analysis showed that the difference in effect observed in PedsQL between the children with and without the diet was even greater. While the children with the advised diet showed similar results, children in the control group showed minimal improvement (data not shown). This indicates that also in children without comorbidities and use of medication, the observed effect of the advised diet was present and that this effect might even be underestimated. However, the group in which the sensitivity analysis was performed was very small and therefore statically relevant conclusions cannot be drawn from this analysis.
Second, laboratory markers were not analyzed to show the effect or the mechanism of the diet on micronutrient deficiencies, as this study focused on the clinical effect. In our study group, laboratory values could not be used, since micro deficiencies are not measurable and patients were excluded once abnormalities were found in the initial laboratory research. It would be interesting to measure laboratory markers, to clarify the mechanism through which the effect of the diet has occurred. A future study could focus on measuring laboratory markers and further quantifying the mechanism of the diet.
A third restraint is the possibility that the period in which children were included in the control group and intervention group affects the results. The control group was studied in the summer (March to August), whereas the intervention group was studied in the winter (September to February). Children visit a general practitioner or pediatrician more often during the winter months than in summer for all kinds of illnesses [51
], and a decrease in vitality is reported during winter in adolescent girls [53
]. This suggests that within both the intervention group and the control group, children could be on the up- or the downswing of a seasonal cycle. For example, a child that starts the diet in February may feel less tired in May regardless of the diet. Overall, it would be interesting (and fair) to evaluate the effect of the advised diet in a simultaneous period and potentially with a longer follow-up.
Fourth, the different components of the diet were valued at the same level. However, this does not reflect the consumption of each of the components, and potentially does not reflect the relative benefits of each of the components. Furthermore, the questionnaire used to measure compliance is not validated.
Finally, parents and children only received advice and an explanation about why the components in the diet are important, rather than a prescription to follow the diet. We used a non-validated questionnaire to check the compliance to the advised diet. However, this questionnaire appeared adequate in other studies in which we used it to check the compliance to the same advised diet [6
]. The “per protocol” analysis showed that the effect of the diet was stronger when it was followed more strictly (“intention to treat” analysis is not shown). Furthermore, a significant relationship between the degree of compliance and the need to sleep was found, which mirrors the results for the total sample.
In a new study, more rigorous check-ups with parents and children to ensure it is followed could increase the effectiveness of the diet.