**7. Why the present finding of the role of theobromine is so revolutionary?**

#### **7.1 Adverse effects of fluoride**

In the past, fluoride is the one that was solely used in the dental profession to prevent dental caries and added to most of the toothpaste. In addition, fluoride has been used a high amount of varnish solution [50] and glass-ionomer cement [51].

Fluoride has been described as the same category of alcohol, nicotine, and lead and advised to avoid them during pregnancy [52]. Fluorosis [53, 54] is very common.

Maternal exposure to fluoride during pregnancy was associated with lower IQ scores in children aged from 3 to 4 years [55]. This is the first report describing the possible effects of lower IQ scores of offspring as a result of maternal fluoride intake. Previously, numerous studies associated with fluoride exposures and lower IQ scores of children were already reported. This phenomenon was observed despite the parents' education and family income in China [56], India [57] and Taiwan [58]. Cognitive alterations in children born from exposed mothers to fluoride could start in early prenatal stages of life and appear later at school age; and likely continue into adulthood [59].

One of the neurodevelopmental disabilities is autism [60] and the decreased secretion of melatonin from the pineal gland alters circadian rhythms and sleep patterns [61].

Another interesting aspect is the relationship between caffeine-containing drinks and fluoride. The higher fluorosis severity was associated with soft drinks and coffee consumption, as most soft drinks contain caffeine [62]. This was explained that the presence of fluoride would remain longer due to the ingestion of caffeine-containing beverages [63].

#### **7.2 Fluoride exposures in early life**

A 6 oz. container of 1500 ppm fluoride toothpastes contains 254.7 mg of fluoride. A one-year-old (8.14 kg) child ingesting less than one-fifth of the contents of the container would possibly exceed a toxic dose [9]. It has been well known that coronary heart disease and related disorders such as stokes, diabetes and hypertension may originate during fetal development [64]. As further examples, overfeeding of newborns tend to lead to obesity in later adult life. Caffeine exposures during the gestation and lactation periods appeared reduced locomotive activity in the later ages of animals [65]. By the undernourishment in utero, intrauterine programming during this period could contribute to the risk of osteoporotic fractures in later life [66]. "Programming phenomena" in the body of early life [67] is explained as nutritional stress during the critical period of growth that causes permanent or long-term changes in the structure or function of the organ.

Unfortunately, certain areas of the U.S. have an incidence of fluorosis of about 70% [54] to 80% [53] in children. These examples stipulate very high incidences of possible fluoride's effects on growing children.

Consider each step. Fluorosis of teeth is a result of the effect of fluoride on ameloblasts cells. The other parts of the organs as well could have been affected by this chemical. Excess fluoride exposures have already been known to cause various diseases described above.

The exposure of fluoride must be not only the excess dose of fluoride but also the duration of exposure and timing [52] such as the critical growth period as explained. Fluorosis has been reported to be associated with the lower performance of neuropsychological tests [68]. Developmental enamel defect is twice as frequently with mental retardation [52]. However, there are not many studies that investigated the relationship between fluorosis in teeth and systemic diseases at the same time. For example, is the incidence of fluorosis related to specific diseases? To answer this question, there is a need for close clinical cooperation between dentistry and medicine in future studies of fluoride.

Patients with fluorosis may develop certain diseases in later life. The growth and development of organs or bodies on the surface could have been minor. However, genetic influences could have already occurred, possibly resulting in a slight alteration of structure or function at the cellular levels [67].

Despite little difference in average levels of tooth decay between fluoridated and unfluoridated water of the same country [69], there are still areas in the US where water is fluoridated and water fluoridation may add a small amount of fluoride into the bodies.

In the body, continuous formation and breakdown have been happening throughout the life cycle. If the periods of the formation far exceed breakdown such as the rapid growth period, minor changes of cellular levels might not appear readily. When the period of breakdown is exceeded in the later stages of life, diseases associated with fluoride exposures in early life could become a root cause of disease in later life [13].

We do not know at this time what kind of diseases, if any, might appear in later life by fluoride exposures in early life. However, early nutritional stresses on the developing fetus cause various diseases [64–66]. The current concept on the number of fluoride exposures in early life and root causes of disease in the future is not an unrealistic hypothesis. If this were proven to be true by future epidemiological studies and/or even one could argue "do we need to wait until such time". The time might have come now to reexamine the routine use of fluoride in dental practice from a fundamental aspect.

*The Contrasting Effects between Caffeine and Theobromine on Crystallization… DOI: http://dx.doi.org/10.5772/intechopen.101116*

#### **7.3 Development of non-fluoride dentifrice**

During the study of caffeine on the effects of developing teeth, we have accidentally discovered that one of the xanthine family, theobromine, showed the opposite effects from caffeine on the crystallization of hydroxylapatite (HAP). Theobromine combined with calcium and phosphorus which is called "rennou" was added to accelerate the crystal formation of non-fluoride dentifrice.

Cacao contains theobromine. Chocolate which comes from cacao has been consumed without any ill effects by humans in the past. Cacao has an interesting history. In 1753, Swedish taxonomer Carl Linnaeus named the cacao plant "theo-broma" which translates to "food of gods". He was a believer in the power of cacao. Ancient Mayans at least 1100 years ago already knew the unique roles of cacao on crystallization and possibly used it to fix jade inside of the enamel. The specific characteristics of theobromine led to the formation of fluoride-free toothpastes.

Theobromine-based dentifrice is revolutionary. This is because space travel in our future, military or even camping where the water supply is most often limited, it is not needed to rinse the mouth with water or just spit after brushing teeth. However, most importantly, even if one swallows it, there are no adverse effects. Theobromine

#### **Figure 12.** *The flow chart shows how non-fluoride dentifrice was developed.*

changes the crystallization dynamics of apatite group species, resulting in fewer and larger crystallites. It likely interacts with ions being deposited at the growing HAP crystal surface. Thus, the ratio of surface area versus volume of the crystals is lowered and dissolution is not as rapid or pronounced as in smaller crystals.

In conclusion, non-fluoride-based dentifrice was introduced for the replacement of fluoride-based toothpastes. Further studies of theobromine-based dentifrice have to be examined as a reliable alternative of the safe replacement of fluoride-based dentifrice. This requires vigorous basic and clinical studies by scientists and clinicians.

So far, all the evidence presented shows that the theobromine is superior to that of fluoride and most importantly, the use of theobromine is safe. The current development of non-fluoride dentifrice is most timely. The flow chart in **Figure 12** was added to summarize the development of this non-fluoride dentifrice.
