Non-superiority of Kakkonto, a Japanese herbal medicine, to a representative multiple cold medicine with respect to anti-aggravation effects on the common cold: a randomized controlled trial.

OBJECTIVE: Kakkonto, a Japanese herbal medicine, is frequently used to treat the common cold not only with a physician's prescription, but also in self-medication situations. This study aimed to examine whether Kakkonto prevents the aggravation of cold symptoms if taken at an early stage of illness compared with a well-selected Western-style multiple cold medicine. METHODS: This study was a multicenter, active drug-controlled, randomized trial. Adults 18 to 65 years of age who felt a touch of cold symptoms and visited 15 outpatient healthcare facilities within 48 hours of symptoms onset were enrolled. The participants were randomly assigned to two groups: one treated with Kakkonto (Kakkonto Extract-A, 6 g/day) (n=209) and one treated with a Western-style multiple cold medicine (Pabron Gold-A, 3.6 g/day) (n=198) for at most four days. The primary outcome of this study was the aggravation of cold, nasal, throat or bronchial symptoms, scored as moderate or severe and lasting for at least two days within five days after entry into the study. RESULTS: Among the 410 enrollees, 340 (168 in the Kakkonto group and 172 in the Pabron group) were included in the analyses. The proportion of participants whose colds were aggravated was 22.6% in the Kakkonto group and 25.0% in the Pabron group (p=0.66). The overall severity of the cold symptoms was not significantly different between the groups. No harmful adverse events occurred in either group. CONCLUSION: Kakkonto did not significantly prevent the progression of cold symptoms, even when prescribed at an early stage of the disease.

Increasing the number of SNP loci does not necessarily improve prediction power at least in the comparison of MTHFR SNP and haplotypes.

BACKGROUND: Rapid advances in genotyping technology have made it possible to easily utilize a large number of genetic markers. According to information theory, an increase in the number of markers provides more information; however, the clinical usefulness does not increase linearly. This study aimed to assess the effect of folic acid supplementation quantitatively in MTHFR haplotypes, and compare its prediction power with that of the C677T single nucleotide polymorphism (SNP) alone. METHODS: The study was a randomized, double-blind, placebo-controlled trial, designed in accordance with the CONSORT statement. The participants were 202 healthy Japanese males who were administered either folic acid at 1 mg/day or a placebo postoperatively for 3 months. The primary endpoint was the total plasma homocysteine levels (tHcy). Stratified analysis by HapMap-based tag SNPs was performed. RESULTS: Of 52 SNPs on the MTHFR gene, 4 SNP loci covering more than 80% of the information were selected, and the haplotypes were estimated. The haplotypes were classified into 3 groups (Hap0, Hap1, and Hap2), on the basis of the number of times the most frequent haplotype was present. The greatest decrease was observed in Hap2 (6.61 micromol/L), compared with the other haplotypes (Hap0, 2.67; Hap1, 2.60) (trend test, P < 0.01). The haplotype information obtained was not more informative than that obtained with grouping by a single SNP, C677T, which strongly influences enzyme activity. CONCLUSIONS: Grouping by the C677T SNP alone was almost as good a predictor of the homocysteine-lowering effects as was grouping by the 4 best SNPs. This shows that increasing the number of typed SNPs does not necessarily provide more information, at least for this gene. A more efficient, cost-informative method for analyzing genomic data is required.

Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation: randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype.

This study aimed at assessing the effect of folic acid supplementation quantitatively in each MTHFR C677T genotype and considered the efficiency of tailor-made prevention of atherosclerosis. Study design was genotype-stratified, randomized, double-blind, placebo-controlled trials. The setting was a Japanese company in the chemical industry. Subjects were 203 healthy men after exclusion of those who took folic acid or drugs known to effect folic acid metabolism. Intervention was folic acid 1 mg/day p.o. for 3 months. The primary endpoint was plasma total homocysteine level (tHcy). In all three genotypes, there were significant tHcy decreases. The greatest decrease was in the TT homozygote [6.61 (3.47-9.76) micromol/l] compared with other genotypes [CC: 2.59 (1.81-3.36), CT: 2.64 (2.16-3.13)], and there was a significant trend between the mutated allele number and the decrease. The tHcy were significantly lowered in all the genotypes, but the amount of the decrease differed significantly in each genotype, which was observed at both 1 and 3 months. Using these time-series data, the largest benefit obtained by the TT homozygote was appraised as 2.4 times compared with the CC homozygote. Taking into account the high allele frequency of this SNP, this quantitative assessment should be useful when considering tailor-made prevention of atherosclerosis with folic acid.