Human studies - 機能性食品素材 - アークレイ - ARKRAY

Mixed herbal extract

Human studies

Ingestion study in prediabetes group11)
(double-blind parallel-group comparison study)

Among the AGEs formed in humans with abnormal glucose metabolism, the increase of 3DG and formation of CML appeared to be inhibited by ingesting AG Herb MIX.

Method
Twenty six adult men and women with prediabetes [random glucose level is between 110 mg/dL and 199 mg/dL while HbA1c(JDS) is between 5.5% and 6.5%] were divided into a group of 13 people ingesting the test food and another group of 13 people ingesting the placebo food. AG Herb MIX or placebo food were ingested at 3,000 mg/day for 8 weeks (double-blind parallel-group comparison study). The blood was collected from each subject before ingesting the test food and after 8 weeks. 3DG and CML were measured as the glycation reaction products in the blood. In addition, this clinical study was performed in accordance with the spirit of the Helsinki Declaration after being approved by an ethics committee. The subjects thoroughly understood the details of the study and voluntarily participated with the relevant consent forms submitted.
Results
During the ingestion period, no adverse event (change in health condition) was recognized in the tests of hepatic function, renal function, and glucose and lipid metabolism functions, etc., that appeared to be caused by the ingestion of AG Herb MIX. Thus, the safety of ingestion as food was verified. Furthermore, the blood AGE levels before the ingestion and after 8 weeks were measured for comparison. The subgroup analysis for the subjects with the blood glucose level at 110 mg/dL or higher showed a trend in which the increase in the blood 3DG level was inhibited in the group ingesting the test food compared with the group ingesting the placebo food (P = 0.094). Similarly, the subgroup analysis for the subjects with HbA1c(JDS) at 5.9% or higher showed a significant decrease in CML (P = 0.048) in the group ingesting the test food compared with the group ingesting the placebo food.

Ingestion study in diabetes patients12) 13)

In patients with type 2 diabetes, the blood levels of glycation products (3DG and CML) were reduced by the ingestion of food containing AG Herb MIX for 12 consecutive weeks. The inhibition of glycation can be expected to prevent protein denaturation, reduce damage to the tissues, and prevent the progress of complications.
Since the ingestion was found to enhance skin elasticity, it is also expected to prevent the aging of skin collagen, and realize anti-aging cosmetic effects, such as improved skin firmness.

Method
Seven adult patients with type 2 diabetes (6 men and 1 woman) were scheduled to ingest hard capsules (3 pieces) containing 600 mg of AG Herb MIX 600 for 12 weeks, once per day, before breakfast.
Physical examinations (body mass index, body fat percentage, etc.), laboratory tests (blood, urine), consultation and interview by physicians, and investigation of living conditions via journals and questionnaires were performed before the ingestion and after 2, 4, 8, and 12 weeks.
Table Subject characteristics before ingestion
Subject Seven adult patients with type 2 diabetes
Age 55.9 ± 6.8 years old
Height 165.0 ± 7.2 cm
Weight 63.7 ± 12.0 kg
BMI 23.5 ± 3.1 kg/m²
Blood glucose level 161.4 ± 48.8 mg/dL
HbA1c (JDS) 7.9 ± 1.4 %

Average ± standard deviation

  1. Blood AGE reduction activity

    The inhibition of glycation is expected to prevent protein denaturation, reduce damage to the tissues, and prevent the progress of complications14).

    Results
    In patients with type 2 diabetes, 3DG and CML, which are bloodborne AGEs, were significantly reduced by the ingestion of 600 mg/day of AG Herb MIX for 12 weeks.
  2. Skin elasticity enhancement activity

    The high blood glucose level maintained in a patient with diabetes tends to decrease the skin elasticity, becoming more pronounced in an age-dependent manner. Therefore, the ingestion of AG Herb MIX is expected to realize anti-aging cosmetic effects, for example, by preventing the aging of skin collagen and retaining skin firmness and elasticity.

    Results
    It is known that the accumulation of AGEs in skin collagen increases with aging in a healthy population and that AGE accumulation in patients with diabetes is greater compared with a healthy population of the same age16). It is also known that skin elasticity is reduced in patients with diabetes compared with non-diabetes patients13) (left figure below).
    The patients with type 2 diabetes were scheduled to consecutively ingest 600 mg/day of AG Herb MIX and their skin elasticity was measured with a Cutometer17). The skin elasticity index increased significantly after 8 weeks (right figure below).
  3. Oxidative stress reduction activity
    Results
    It has been confirmed that the consecutive ingestion of AG Herb MIX can inhibit oxidation of living bodies through its antioxidant ability.

Inhibitory activity on skin AGE accumulation17)

It has been confirmed that the ingestion of AG Herb MIX can inhibit the formation of AGEs in the skin. Since the AGEs were found to increase when the ingestion was suspended, consecutive ingestion is recommended.

Method
A group of 8 healthy adult men and women and a group of 4 with diabetes or high blood glucose levels were scheduled to ingest test food containing 600 mg/day of AG Herb MIX as well as ginger and Japanese pepper for 12 consecutive weeks. Before the ingestion and after 8 and 12 weeks, the fluorescence value (AF) derived from the AGEs in the skin was measured with an AGE Reader to determine the AGE accumulation19). In addition, this clinical study was performed in accordance with the spirit of the Helsinki Declaration after being approved by an ethics committee. The subjects thoroughly understood the details of the study and voluntarily participated with the consent submitted.
Result
During the ingestion period, no adverse event (change in health conditions) was recognized in the tests of hepatic function, renal function, and glucose and lipid metabolism functions, etc., that appeared to be caused by the ingestion of AG Herb MIX. Thus, the safety of ingestion as food was verified. In addition, the accumulation of AGEs in the skin of the healthy group was significantly decreased after 8 weeks (P = 0.035) and 12 weeks (P = 0.020) compared with the accumulation before the ingestion. In the group with diabetes or high blood glucose levels, 3 out of 4 subjects also showed a decrease in the accumulation. Since the fluorescent AGEs contain compounds such as crossline and pentosidine, which are involved in cross-linking of proteins, it is suggested that the ingestion of AG Herb MIX can inhibit aging such as stiffening caused by glycative cross-linking of skin proteins.

Inhibitory activity on skin AGE accumulation 19)
(low-dose pilot study)

Out of 7 healthy adult men and women, 3 ingested 100 mg/day and 4 ingested 300 mg/day of AG Herb MIX for 12 consecutive weeks. Before the ingestion and after 12 weeks, the fluorescence value (AF) derived from the AGEs in the skin was measured with an AGE Reader to determine the AGE accumulation21). The results showed the accumulation of AGEs in the skin decreased for both the 100 mg/day and 300 mg/day ingestion groups. The fluorescent AGEs contain compounds such as crossline and pentosidine, which are involved in cross-linking of proteins22). Previously, it was confirmed that the accumulation of AGEs in the skin decreased after the ingestion of test food containing 600 mg/day of AG Herb MIX as well as ginger and Japanese pepper for 12 weeks23). This new study suggests that ingesting 100 mg/day or more of AG Herb MIX can inhibit aging such as stiffening caused by glycative cross-linking of skin proteins.

Validation test for skin beautification activity by anti-glycation 23)

The ingestion of AG Herb MIX inhibited yellowing and browning of the skin color. In the group ingesting the test food, levels of the bloodborne AGE intermediate 3-deoxyglucosone (3DG) were significantly decreased. Therefore, two-fold skin beautification activity is expected: the inhibition of glycation can help recovery from “yellow dullness” or “browning” of the skin and the herbal ingredients can improve the complexion.

Method
The subjects were 24 Japanese women who were over 40 but under 65, with increased AGE deposition on the skin (determined with an AGE Reader). They were divided into an AG Herb MIX group (ingesting the test food) of 12 people and a placebo group of 12 people. The test food was ingested as a capsule-like food containing 100 mg/day of AG Herb MIX for 12 weeks. A placebo-controlled double-blind randomized parallel-group comparison study was performed, including blood testing, skin-related measurements, and interviews, before the ingestion and after ingesting for 8 and 12 weeks. In addition, this study was performed after being approved by an ethics committee (clinical study registration ID: UMIN000015242).
Result
In all cases, significant reductions were found for the group ingesting the test food compared with the placebo group in the melanin index of the upper arm skin (test food group: -0.04, placebo group: +0.01, p = 0.009) and the color difference b* (yellow) in the upper arm skin (test food group: -0.66, placebo group: +0.16, p = 0.025). In addition, a significant reduction in the value characterizing brown spots on the facial skin was found in the group ingesting the test food after 12 weeks of ingestion compared with the value before the ingestion (48.39 to 46.49, p = 0.005). In a subgroup of healthy individuals excluding 2 people with suspected diabetes (test food group: 10, placebo group: 12), 3DG was significantly decreased in the group ingesting the test food after 12 weeks compared with before the ingestion (16.96 ng/mL to 13.73 ng/mL, p = 0.043). In addition, the increase in the hemoglobin oxygen saturation index of the cheek skin (one of the complexion indicators) was significantly larger for the test food group compared with the placebo group (test food group: +7.38, placebo group: +4.36, p = 0.020). This suggests AG Herb MIX may not only reduce yellowing and browning of the skin color by inhibiting 3DG formation, but may also improve the complexion with its herbal ingredients.

Results of the color difference measurement and skin image diagnosis with VISIA (excerpt)

Changes in the visual judgments and actual measured values are excerpted from the human study for validating the skin beautification activity. The color difference measurement showed reductions in the melanin index and b*, and an increase in L*. The VISIA image diagnosis performed on the same subjects showed improvements in the values for the brown and general spots. Confirmation of the actual changes using pictures shows an overall reduction in the spots, fading of individual spots, and overall brightening of the skin.
Although this is only one example, these results suggest that a whitening effect can be expected from ingesting AG Herb MIX.