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If the demand for nicotine is robust, the policy problem is to move to ways of using it that are much less harmful than the dominant method, smoking tobacco

Similarly, a European population-based study showed a significant decrease in protamine 2 (P2) concentrations in smokers, which subsequently caused an abnormal elevation of the P1:P2 protein ratio [158]

Geographical differences in the trends were also noted, with Latin America and high-income North America, Australia, Colombia, and Canada showing the greatest decline, and middle-SDI regions, especially East Asia, showing a slight upward trend

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Sulistyowati believes the problem is worse in rural areas and among poorer populations