**2. Results**

#### *2.1. Prevalence of H. Pylori Infection AccordingtTo the Frequency of Mozuku Consumption and Age*

The relevance of mozuku consumption and age to *H. pylori* infection is shown in Table 1. Regarding age, *H. pylori* infection was detected in 60.0%, 58.7%, 61.9%, 77.8%, and 88.5% of participants aged 20–29, 30–39, 40–49, 50–59, and ≥60 years old, respectively.

According to logistic regression analysis, age was a significant risk factor for *H. pylori* infection, as the risk of infection was significantly higher in patients ≥40 years old than in those <40 years old. Mozuku consumption was not a significant risk factor for *H. pylori* infection (Table 2).


**Table 1.** *Helicobacter pylori* infection according to the frequency of mozuku consumption and age.

20's: 20–29 years old, 30's: 30–39 years old, 40's: 40–49 years old, 50's: 50–59 years old, ≥60's: over 60 years old. n = number of subjects.

**Table 2.** Relevance of age and mozuku consumption to *Helicobacter pylori* infection: logistic regression analysis.



#### *2.2. Urinary Fucoidan Values before and after Fucoidan Ingestion*

In all subjects, the urinary fucoidan values significantly increased 3, 6, and 9 h after fucoidan ingestion compared to the basal values (Table 3). The urinary fucoidan values were significantly higher at 6 and 9 h than those at 3 h. A significant difference was not observed in the urinary fucoidan values between the group that regularly ate mozuku and group that rarely ate mozuku.


**Table 3.** Time course of urinary fucoidan.

All data are presented as mean ± SD. Different letters indicate a significant difference as follows: a compared to the basal value (*p* < 0.01). b Compared to the fucoidan values at3h(*p* < 0.01). n = number of subjects.

#### *2.3. Basal Levels (before Ingestion) of Fucoidan*

Among subjects who rarely ate mozuku, the basal fucoidan levels were significantly lower in the *H. pylori*-negative group than in the *H. pylori*-positive group. Among *H. pylori*-negative subjects, the basal fucoidan levels were significantly lower in those who rarely ate mozuku than in those who ate mozuku 1–3 times weekly, once monthly, or once every 2–3 months. Conversely, the basal fucoidan levels were not affected by the frequency of mozuku consumption or age in *H. pylori*-positive subjects (Table 4).

**Table 4.** Basal fucoidan levels according to the frequency of mozuku consumption in *Helicobacter pylori*-negative and *Helicobacter pylori*-positive subjects.


All data are presented as mean ± SD. Different letters indicate a significant difference as follows: a compared to *H. pylori*-negative subjects who hardly ate mozuku (*p* = 0.01); b compared to *H. pylori*-negative subjects who hardly ate mozuku (*p* = 0.03); c compared to *H. pylori*-negative subjects who hardly ate mozuku (*p* = 0.03). n = number of subjects.

#### *2.4. Relationship between H. pylori Titers and Basal Fucoidan Levels*

Among *H. pylori*-positive subjects, a significant positive correlation existed between *H. pylori* titers and basal fucoidan levels in participants <40 years old who ate mozuku at least once monthly. A significant correlation between *H. pylori* titers and basal fucoidan levels was not found in participants aged ≥40 years irrespective of the frequency of mozuku consumption (Figure 1).

**Figure 1.** Relationship between *Helicobacter pylori* titers and basal fucoidan levels according to the frequency of mozuku consumption and age in among *H. pylori*-positive subjects. (**A**) Subjects aged <40 years who ate mozuku at least once a month. (**B**) Subjects aged ≥40 years who ate mozuku at least once a month. (**C**) Subjects aged <40 years who ate mozuku once every 2–3 months or less. (**D**) Subjects aged ≥40 years who ate mozuku once every 2–3 months or less. n = number of subjects, r = correlation coefficient, n.s = not significant.

#### *2.5. Maximum Absorption of Fucoidan (*Δ*Max Fucoidan Value)*

Urinary fucoidan was detected in 252 of 259 subjects following a single oral dose of 3 g. The ΔMax fucoidan values exhibited a wide distribution, ranging from 0 to 273.6 ng/mL. Among the participants in whom urinary fucoidan was not detected, three rarely ate mozuku, one ate mozuku once every 2–3 months, and three ate mozuku once monthly.

Table 5 shows the relevance of *H. pylori* infection and age to the ΔMax fucoidan values. The ΔMax fucoidan values in all subjects were similar between *H. pylori*-positive and *H. pylori*-negative subjects. Compared with the values in *H. pylori-negative* subjects, the ΔMax fucoidan values of *H. pylori*-positive subjects tended to be higher in subjects in their 20s and 30s and lower in those in their 40s and 50s (data not shown). To determine relevance of age to fucoidan absorption, the subjects were divided into two age groups (<40 and ≥40 years).

ΔMax fucoidan values were significantly lower in subjects aged ≥40 years than in younger subjects among *H. pylori*-positive participants. No effect of age on ΔMax fucoidan values was observed among *H. pylori*-negative subjects. No significant difference of ΔMax fucoidan values was found according to the presence of *H. pylori* infection in either age group.


**Table 5.** Comparison of ΔMax fucoidan values by age.

All data were presented as mean ± SD. a There is a significant difference (*p* < 0.01) compared to H. pylori-positive subjects aged <40 years. n = number of subjects, y.o.: years old; *P* = *P* value.

#### *2.6. Relevance of H. Pylori Infection and Mozuku Consumption to Fucoidan Absorption*

In a comparison between participants aged ≥40 years and those aged <40 years, the ΔMax fucoidan values were decreased by regular mozuku consumption in *H. pylori*-positive subjects but not in *H. pylori*-negative subjects (Table 6). Specifically, ΔMax fucoidan values were lower in *H. pylori*-positive subjects aged ≥40 years who ate mozuku at least once a month than in those who ate mozuku less frequently. Subsequently, the subjects were divided into groups based on the frequency of mozuku consumption, and the relevance of mozuku consumption to ΔMax fucoidan values was elucidated (Table 7).

**Table 6.** Relevance of *Helicobacter pylori* infection, frequency of mozuku consumption, and age to ΔMax fucoidan values.


All data are presented as mean ± SD. a Compared to H. pylori-negative subjects aged ≥40 years who hardly ate mozuku (*p* < 0.01). n = number of subjects, n.s: not significant; y.o.: years old.

**Table 7.** Relevance of *Helicobacter pylori* infection and age to ΔMax fucoidan values according to the frequency of mozuku consumption.


All data are presented as mean ± SD. 1) Regularly consumed mozuku: 1–3 times weekly + once every 2 weeks + once monthly; 2) rarely ate mozuku: once every 2–3 months + hardly ate. a Compared to *H. pylori*-positive subjects aged <40 years who ate mozuku at least once monthly (*p* = 0.03). b Compared to *H. pylori*-positive subjects aged ≥40 years who ate mozuku once every 2–3 months or less (*p* = 0.01). c Compared to *H. pylori*-negative subjects aged ≥40 years who ate mozuku at least once monthly (*p* = 0.01). n = number of subjects, y.o = years old.

Among *H. pylori*-positive subjects who ate mozuku at least once a month, ΔMax fucoidan values were significantly lower in those aged ≥40 years than in those aged <40 years. In addition, among *H. pylori*-positive subjects aged ≥40 years, the ΔMax fucoidan values were significantly lower in those who regularly consumed mozuku than in those who rarely ate mozuku. In addition, the ΔMax fucoidan values were significantly different between *H. pylori*-positive (16.8±20.8) and *H. pylori*-negative subjects (32.1 ± 17.6) among those who ate mozuku at least once a month. However, no difference in ΔMax fucoidan values was noted according to age or frequency of mozuku consumption among *H. pylori*-negative participants.

#### *2.7. Relationship between the Basal and* Δ*max Fucoidan Values in H. Pylori-Positive Subjects*

Among *H. pylori*-positive subjects who regularly consumed mozuku, a significant positive correlation between the basal and ΔMax fucoidan values was found for those aged <40 years but not those aged ≥40 years. No significant correlation was found between the basal and ΔMax fucoidan levels among participants who rarely ate mozuku (Figure 2).

In addition, no significant correlations were found between the basal and ΔMax fucoidan levels in *H. pylori*-negative subjects regardless of the frequency of mozuku consumption (data not shown).

**Figure 2.** Relationship between basal fucoidan values and the maximum absorption of fucoidan (ΔMax fucoidan values) according to the frequency of mozuku consumption and age in *Helicobacter pylori*-positive subjects. (**A**) Consumption of mozuku at least once monthly among subjects aged <40 years (**B**) Consumption of mozuku at least once monthly among subjects aged ≥40 years (**C**) Consumption of mozuku once every 2–3 months or less among subjects aged <40 years (**D**) Consumption of mozuku once every 2–3 months or less among subjects aged ≥40 years. n = number of subjects, r = correlation coefficient, n.s = not significant.
