Determination of maintenance Jarlsberg® cheese dose to keep the obtained serum osteocalcin level; a response surface pathway designed de-escalation dose study with individual starting values

Abstract

<p class="abstract"><strong>Background:</strong> Daily maximum effective dose (MED) of Jarlsberg® increased the serum osteocalcin (tOC) level, vitamin K2 and affected the lipid pattern positively. The aim of the study was to estimate and verify a daily maintenance dose.</p><p class="abstract"><strong>Methods:</strong> 12 healthy female volunteers (HV) were included in a de-escalation study after a six week run-in period on the daily MED of 57 g Jarlsberg® cheese. A 3-level within-patient response surface pathway (RSP) design with individual starting values was developed. Another 12 HVs were included in a new study with a six week run-in period on MED followed with six weeks on the estimated maintenance dose. All HVs were premenopausal female between 20 and 52 years of age. The main variable in the studies was the tOC level.</p><p class="abstract"><strong>Results:</strong> tOC, cOC and the vitamin K2 variants increases significantly (p<0.01) during the run-in period on daily MED of Jarlsberg® in both studies. The maintenance daily dose was estimated to 45 g (95% CI: 38-52 g/day) and used in the new study. The tOC level was reduced from 19.8 ng/ml (95% CI: 12.0-27.6) obtained in the run-in period to 18.5 ng/ml (95% CI: 11.7-25.3) during the maintenance part. This represents a reduction of 6.6%. The sum of vitamin K2 variants changed from 0.58 ng/ml on MED of Jarlsberg® to 0.59 ng/ml (95% CI: 0.37-0.82) during the maintenance period.</p><p class="abstract"><strong>Conclusions: </strong>Daily MED of Jarlsberg® cheese increases tOC, cOC and the vitamin K2 level. The maintenance Jarlsberg® dose was estimated to 45 g/day and verified as sufficient.</p>

Effect on bone anabolic markers of daily cheese intake with and without vitamin K2: a randomised clinical trial

“…In the J-group, the tOC and cOC increased significantly confirming the results in the two previous dose-response-studies 10 11. In the C-group the tOC was slightly, but not significantly reduced after the first 6 weeks.…”

“…In the dose-response study, the level of vitamin K 2 increased with increasing cheese dose whereas tOC and cOC showed a maximum at 57 g cheese a day and falling trends above this dose 10. A similar pattern was also detected in the dose de-escalation study 11. This should not be the case if vitamin K 2 was the only factor which increases tOC.…”

“…There was a high degree of covariation between the rise of tOC and vitamin K 2 . The calculated correlation between these two variables is significant, but substantially weaker than the graphical illustration may indicate, and was obvious in the previous studies 10 11. In the dose-response study, the level of vitamin K 2 increased with increasing cheese dose whereas tOC and cOC showed a maximum at 57 g cheese a day and falling trends above this dose 10.…”

“…The maximum efficacy dose (MED) of Jarlsberg in order to obtain increased vitamin K 2 status, measured as osteocalcin carboxylation and total serum osteocalcin (tOC) level was estimated to 57 g/day 10. These results were confirmed in a recent clinical study on the same study population 11. The MED of 57 g/day Jarlsberg cheese was verified to increase the vitamin K 2 status and tOC level 11.…”

“…Vitamin K in cheese and blood samples was analysed as described previously 10 11. The cOC and the undercarboxylated osteocalcin (ucOC) were measured in plasma by immunoassays kits (Takara Bio, Ōtsu, Japan) by Vitas AS.…”