Compliance was assessed by questionnaire and by pill count at the end of each visit. The baseline questionnaire assessed patient's demographics, BP and other medications, supplements, family history of cardiovascular and chronic diseases. Tolerability of trial capsules was assessed at each 4-weekly appointment using our previously developed questionnaire 1 , 2.
The week questionnaire audited medication, and assessed acceptability of trial capsules and blinding success. The displays of the sphygmomanometers was positioned away from the patient to assure blinding to the BP readings. BP was recorded as three serial measurements at intervals of 30 s. The mean of the three BP measurements was used in the analysis.
If a BP reading deviated by more than 10 mm Hg from the average reading, the BP reading on that arm was repeated. With the Mobil-O-Graph device we also assessed central hemodynamic measures, including central blood pressure, pulse-wave-velocity PWV , pulse pressure, and arterial stiffness at baseline, 4, 8, and 12 weeks.
The Mobil-O-Graph, used in our previous trial 3 , is a brachial non-invasive device which takes a 10 s snapshot of the radial arterial pressure wave and derives the ascending aortic pressure wave, providing central cardiovascular measurements.
Here PWV is indirectly derived by a computerized algorithm calculated from the brachial pulse. As PWV, a measure for arterial stiffness and a strong predictor of cardiovascular morbidity, is more accurately measured directly by the assessment of the distance traveled over time from carotid to femoral artery 7, we also used the validated SphygmoCor Xcel device Atcor Medical, AUS for PWV.
Here, the patient is in a supine position, and the distance from the carotid to femoral pulse is measured, and the time for the pulse wave to travel from carotid to femoral artery is assessed by applanation tonometry. Descriptive analysis was carried out for baseline variables. Normality of data distribution was assessed by the Shapiro—Wilks test. Differences between the groups at 12 weeks compared to baseline were assessed by chi-square test for binominal variables, and by one-way ANOVA with Bonferroni adjustment for continuous and normally distributed variables.
Primary analysis was conducted with all participants following protocol, excluding data points owing to BP medication change. We compared Vitamin B12 levels to BP change between groups by scatterplots. Results were presented as colony-forming-units CFU per gram of stool of 21 bacterial species, grouped into four main phyla: Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria phyla.
Correlations between BP change and gut microbiota change were analyzed by the non-parametric Spearman correlation. The trial was conducted in Melbourne, Australia between May and October A total of 57 patients were screened for eligibility, 52 patients were enrolled in the trial and randomly allocated to the garlic or the placebo group.
Three patients withdrew due to illness unrelated to the trial, with a total of 49 patients completing the trial in Dec Full data analysis was available for all outcome measures by October , with some missing data due to a variety of reasons outlined in Figure 1.
Potential confounding factors, including baseline SBP, were accounted for in the analyses. About half of the participants took other prescription medications, and did not change these over the period of the trial Table 1. None of the participants reported a substantial change in diet or exercise regimen throughout the trial period. Our sample was a homogenous group of people with uncontrolled hypertension and of similar age.
Diastolic blood pressure DBP was reduced on average by 9. Figure 2. The trajectory of blood pressure change over time within both groups is in line with the findings in previous trials 1 — 3 , whereby blood pressure dropped slightly from baseline in the placebo group due to reduced whitecoat effect and familiarization with the trial staff and environment 36 — 38 , but did not decrease to the same extent as in the garlic group, resulting in a statistically significant mean BP difference between the groups.
However, the small number in the subgroup of participants not taking standard BP medication limited interpretability of findings. In summary, Kyolic aged garlic extract significantly lowered central blood pressure, pulse pressure and adjusted pulse wave velocity, an indicator for arterial stiffness Table 2.
Vitamin B12 is one of the important co-factors in the mechanism of action for blood pressure reduction amongst other B-complex vitamins and genetic factors As there is a large proportion of adults in Australia below the optimal levels of Vitamin B12 13 , we explored whether a low Vitamin B12 level may be involved in the responsiveness to garlic in hypertensives.
Figure 3. Scatterplot SBP changes over time compared to average levels of Vitamin B12 mean levels at baseline and 12 weeks by group. Figure 4 illustrates the relative abundance at baseline Figure 4A and at 12 weeks Figure 4B in both groups as stacked bar chart, and Figure 4C illustrates the change in relative abundance over time by group. Interestingly, there was a marked increase of Lactobacillus Firm6 bacteria and Clostridia species Firm3 in the garlic group, while Faecalibacterium prausnitzii Firm5 markedly increased in the placebo group.
All marked observed changes were in the Firmicutes phylum albeit not statistically significant between the groups Figure 4 , Table S1. Figure 4. There was a small but statistically insignificant shift in microbial diversity with an increase in diversity in the garlic group, while there was a small decrease in diversity in the placebo group over time Figure 5. Figure 5. Shannon microbial diversity at baseline blue , 12 weeks green , and change over time beige by group garlic vs.
To assess whether there were any statistically significant correlations between changes in blood pressure and microbiota, we used Spearman correlation. No significant correlations were obtained between BP and observed microbiotic changes within the groups.
However, the observed changes in the Firmicutes phylum in the garlic group with an increase in numbers in Clostridia and Lactobacillus species and a decrease in F. Observed microbiotic changes in the placebo group followed an inverse direction compared to the garlic group, while F. After excluding outliers, e. In contrast, a greater decrease but not statistically significant decrease in IL-6 was observed in the placebo group.
In subsequent subgroup analyses we compared groups with high or low levels of inflammatory markers at baseline. In the subgroup with high IL-6 levels, there was a greater reduction of IL-6 in the placebo group, albeit not statistically significant Table 4.
Blinding was successful, with two-thirds Our trial suggests Kyolic aged garlic extract to be effective in reducing blood pressure in patients with uncontrolled hypertension, in line with our previous trials 1 — 3. A dosage of two capsules daily containing 1. Subgroup analysis of participants taking standard BP medication revealed a slightly greater reduction in SBP by To explore potential underlying factors of individual responsiveness to garlic supplementation, we tested for vitamin B12 levels in this trial.
Vitamin B12 is one of the important co-factors implicated in the methylation and H 2 S signaling pathway by which garlic reduces blood pressure, and may serve as a proxy marker for other underlying deficiencies in vitamin B6, vitamin B2, and folate, also essential co-factors in H 2 S production 12 , AGE has demonstrated in numerous clinical studies to support overall cardiovascular health by reducing many risk factors for heart disease e.
Our AGE has also been shown in clinical studies to show favorable impact in areas of immune function, gingivitis, stress and gut microbiota.
As with any dietary supplement, results vary from individual to individual. We generally recommend taking the product for one to three months before evaluating. Share Online. Printer Friendly. Q What is the source of your gelatin capsules used in your Kyolic products? Q Where are your Kyolic products manufactured?
Q When should I expect results when taking your Kyolic products? The University of Maryland Medical Center states that fresh garlic, when added to the diet with fresh vegetables and fruit, may reduce the chances of developing colon cancer. Other research has suggested that consuming large quantities of the herb may help to fight intestinal parasites, although research is still limited regarding this effect in humans.
Furthermore, studies conflict on whether fresh garlic can help to kill ulcer-causing bacteria. Other research confirms that applying garlic to fungal skin conditions can improve symptoms. Few studies have actually compared the efficacy of fresh garlic versus aged garlic extract for specific conditions.
In , a study published in the "Archives of Internal Medicine" determined that neither fresh nor aged garlic supplements had statistically significant effects on moderately high cholesterol levels after six months. Prior to that, a study reported in the "Journal of Nutrition" stated that aged garlic extract supplements did in fact lower cholesterol in subjects.
Talk to your doctor before taking any kind of garlic supplement. Aged Garlic vs. The biosynthesis and accumulation of these sulfur-containing compounds become the most active in one to two months prior to the harvest 4.
Other constituents, such as common amino acids, carbohydrates, proteins and lipids, are also actively produced and accumulate during the same period when garlic bulbs grow rapidly 4. The resulting mature garlic is harvested from early summer through mid-summer to be used for various purposes, such as in foods, seasonings, medicinal treatments and others 4. Chemical structures of compounds found in garlic and aged garlic extract. Chemical structures of compounds in A raw garlic and B-D aged garlic extract.
E Chemical structures of compounds in Maillard reaction-relating compounds. In the manufacturing of garlic products, raw garlic is processed through various methods, such as crushing, slicing, freeze-drying, heating, soaking, macerating, steam distillation, etc. Some constituents in raw garlic change to other compounds by processing, and the physical and chemical properties of preparation depend on the processing methods 5 — 7.
Garlic oil, a yellow-brown-colored liquid with a sharp characteristic smell, is produced by the steam distillation method and its constituents are mainly composed of diallylpolysulfides DASn Fig. Oil macerate, a liquid form with a characteristic smell, is produced by the soaking of garlic in vegetable oil, and its constituents include unique sulfur compounds, ajoenes and vinyldithiins Fig. The biological properties of garlic have been evaluated by several researchers and garlic has been shown to have useful biological activities for the promotion of human health 6 , 10 , 11 , The compounds present in AGE can be produced via various and complex reactions.
In particular, the complex chemistry of sulfur-containing compounds is considered to contribute mostly to the diversity of the constituents found in AGE.
In order to reveal the production mechanisms of characteristic compounds found in AGE during the aging process, the model reaction and the laboratory experiments mimicking the aging process were conducted under the hypothesis of production mechanisms of identified compounds leading from the analytical results of key compounds fluctuations.
In this review, we present the changes of some characteristic compounds found in AGE during the aging process, and discuss their production mechanisms involving various chemical and enzymatic reactions. We also discuss associations between products and their precursor materials. GSAkCs abundantly exist in garlic cloves during the dormant period, from the time after harvest in summer to before sprouting in autumn Figs. However, the contents of these constituents decease when garlic cloves sense a decrease in environmental temperature, which acts as a stimulation signal to break the dormancy period, and they are gradually transformed into SACOs 13 , Although only a trace amount of SAC is detected in raw garlic, the content of this compound increases during the processing of garlic 13 , Sun et al reported that GGT activity derived from garlic was significantly enhanced by glucose Glc , aspartic acid Asp and cysteine Cys Saccharides in raw garlic are mainly fructans that are composed of 1—2 glycosyl linkage polymer of fructose Fru with the reduction end of Glc Fig.
Raw garlic contains almost no free Glc; however, its content in AGE gradually increases with the progress of aging by the hydrolysis of fructan, including the release of Glc in the reduction end of fructan. The Asp content in raw garlic has been shown to be 0. These constituents can promote the activity of GGT during the aging process. Constituents in raw garlic and production pathways of characteristic compounds in aged garlic extract. A Constituents in raw garlic.
C Production mechanism of S-alk en ylcyteine by enzymatic reaction and compounds produced. E Hydrolysis of polysaccharide, fructan. F Production mechanism of Amadori compounds by the Maillard reaction and compounds produced.
G Production mechanism of S-allylmercaptocysteine. H Hydrophobic compounds derived from alliin and their transformed compounds. Combination of block arrows and compound names indicate the providing of raw materials to the reaction pathways involved.
Please refer to the corresponding names spelled out and the structures shown in Fig. In previous studies, when SMC, SAC and trans -S1PC were orally administered to experimental animals, they were rapidly absorbed, and exhibited excellent bioavailability, remaining stable in body fluids 16 , The beneficial effects of these compounds have been documented by a number of researchers 13 , 18 — Allicin, a transformation product of alliin, subsequently generates various compounds, such as DASn, ajoenes, vinyldithiins, etc.
They have a low absorption rate and remain unstable in the body 25 — The overall yields of these hydrophobic compounds are small as they transform into various compounds and their source compound in raw garlic is only alliin, i. The endogenous enzyme GGT which produces S -alk en yl-cysteines is considered to be one of key factors for the diversity of constituents in AGE. The generation of water-soluble cysteine derivatives during the aging process may contribute to the promotion of human health.
The chemical and biological properties of S1PC have not been evaluated for a long period of time, although S1PC was found to be present in garlic preparations in the early s Recently, the fluctuation of its cis - and trans -form in AGE has been reported The model reaction to confirm the isomerization of S1PC was previously conducted using cis - and trans -form of S1PC organochemically synthesized on the chronological analysis of nuclear magnetic resonance NMR spectrum changes.
While only one propenyl group form of signals was observed in each test sample at day 0, both proton signals of cis - and trans -S1PC in the test substances at day 30 were detected with almost the same intensities According to the results of chronological evaluation, the isomerization reaction was confirmed to occur reversibly Fig. Divalent sulfides have an electron-releasing conjugative effect when unsaturated group or carbonium ion directly binds to sulfur 32 , Although the biological properties of cis -S1PC have not yet been reported, the advances being made in garlic chemistry may soon precisely clarify these properties, including the associations between the biological activities and structure difference of cis - and trans -form.
Furthermore, the balance of cis - and trans -form content may serve as a marker of the aging process, as the content of cis -form compound in fresh garlic is very small compared to that of trans -form; however, its amount increases with time.
The contents of these dipeptides in AGE decrease with the increasing S -alk en ylcysteine content Fig. Kasai et al suggested that GGSMC is a useful index compound for the quality control of imported Vigna radiata seeds and Vigna mungo seeds
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