Oral administration of French maritime pine bark extract (Flavangenol^®) improves clinical symptoms in photoaged facial skin

Figures & data

Figure 1 Schematic outline of part 1 and part 2 of study using low-dose pine bark extract.

Abbreviation: PBE, pine bark extract.

Table 1 Baseline demographics of randomized groups (phase I, low-dose PBE trial)

Characteristics	Group I N = 38	Group II N = 39	P value
Age (yrs)	39.6 (8.3)	33.8 (6.5)	0.66
ITA (degrees)	30.9 (8.3)	28.6 (5.4)	0.44

Note: Mean (SD).

Abbreviations: ITA, individual topology angle; PBE, pine bark extract.

Table 2 Score assessments of questionnaire survey (high-dose PBE trial, N = 24)

Symptoms	Improved	Unchanged	Aggravated
Age spots	7 (29)	16 (67)	1 (4)
Wrinkles	7 (29)	17 (71)	0 (0)
Roughness (dry skin)	9 (38)	15 (63)	0 (0)
Roughness (other than dry skin)	13 (54)	9 (38)	2 (8)

Notes: Number of patients (%). The score changes were evaluated as compared with baseline of symptoms before PBE administration.

Abbreviation: PBE, pine bark extract.

Table 3A Score assessments of questionnaire survey for group I (phase I, low-dose PBE trial, N = 38)

Symptoms	Improved	No change	Aggravated
Solar lentigines	12 (32)	24 (65)	1 (3)
Mottled pigmentation	14 (38)	22 (59)	1 (3)
Roughness (dry skin)	8 (23)	26 (74)	1 (3)
Roughness (other than dry skin)	5 (14)	28 (78)	3 (8)
Wrinkles	1 (3)	33 (97)	0 (0)

Notes: Number of patients (%). The score changes were evaluated as compared with baseline of symptoms before PBE administration.

Abbreviation: PBE, pine bark extract.

Table 3B Score assessments of questionnaire survey for group II (phase I, low-dose PBE trial, N = 39)

Symptoms	Improved	Unchanged	Aggravated
Solar lentigines	13 (33)	25 (64)	1 (3)
Mottled pigmentation	10 (26)	27 (71)	1 (3)
Roughness (dry skin)	11 (30)	24 (65)	2 (5)
Roughness (other than dry skin)	7 (18)	26 (68)	5 (13)
Wrinkles	4 (11)	31 (84)	2 (5)

Notes: Number of patients (%). The score changes were evaluated as compared with baseline of symptoms before PBE administration.

Abbreviation: PBE, pine bark extract.

Table 4 Score assessment of questionnaire survey for 18-month PBE administration (phase II, low-dose PBE trial, N = 21)

Symptoms	Improved	Unchanged	Aggravated
Solar lentigines	9 (43)	12 (57)	0 (0)
Mottled pigmentation	9 (43)	10 (48)	1 (5)
Roughness (dry skin)	8 (38)	10 (48)	1 (5)
Roughness (other than dry skin)	4 (19)	12 (48)	2 (10)
Wrinkles	4 (19)	16 (76)	0 (0)

Note: Number of patients (%).

Abbreviation: PBE, pine bark extract.

Table 5 Physical examination scores (phase I, low-dose PBE trial)

Symptoms	Group	Baseline	12 weeks	24 weeks
Solar lentigines	I	2.8 (0.8)	2.3 (0.6)c,d	2.3 (0.5)c
	II	2.7 (0.7)	2.7 (0.7)	2.4 (0.8)b
Mottled pigmentation	I	2.5 (0.6)	2.1 (0.5)c	1.9 (0.4)c
	II	2.2 (0.7)	2.2 (0.6)	1.9 (0.6)a
Roughness	I	2.2 (0.7)	1.8 (0.6)a,d	1.9 (0.6)
	II	1.9 (0.8)	2.1 (0.8)	1.5 (0.6)a
Wrinkles	I	2.2 (0.7)	2.0 (0.6)a	1.9 (0.6)b
	II	2.1 (0.5)	2.1 (0.5)	2.0 (0.5)
Swelling	I	1.4 (0.8)	1.3 (0.5)a	1.2 (0.4)a
	II	1.4 (0.6)	1.4 (0.6)	1.3 (0.4)

Notes: Mean score (SD). The efficacy of PBE was assessed by analyzing the change from baseline scores. Reliability was assessed by Wilcoxon signed rank test.

a P < 0.05,

b P < 0.01,

c P < 0.001. Reliability was assessed by Mann–Whitney U test between group I and group II.

d P < 0.05 (group I vs group II).

Abbreviation: PBE, pine bark extract.

Figure 2 Before (left) and 6 months after (right) treatment of photodamaged skin with oral pine bark extract.

Table 6 Physical examination scores (phase II, low-dose PBE trial, N = 21)

Symptoms	Baseline	24 weeks	18 months
Solar lentigines	2.8 (0.8)	2.1 (0.4)b	1.9 (0.3)c
Mottled pigmentation	2.3 (0.6)	1.8 (0.4)b	1.6 (0.5)b
Roughness	2.0 (0.9)	1.5 (0.6)a	1.3 (0.5)b
Wrinkles	1.6 (0.7)	1.4 (0.5)	1.3 (0.5)a
Swelling	2.0 (0.8)	1.7 (0.7)a	1.6 (0.5)a

Notes: Mean score (SD). The efficacy of PBE was assessed by analyzing the change from baseline scores. Reliability was assessed by Wilcoxon signed rank test.

a P < 0.05,

b P < 0.01,

c P < 0.001.

Abbreviation: PBE, pine bark extract.

Table 7A Overall efficacy rate after 24-week low-dose PBE administration (phase I, low-dose PBE trial)

Outcome	Group I	Group II
Markedly improved	1 (3)	1 (3)
Moderately improved	16 (42)	9 (23)
Slightly improved	16 (42)	18 (46)
Unchanged	5 (13)	11 (28)
Aggravated	0 (0)	0 (0)
Total	38	39

Note: Number of patients (%).

Abbreviation: PBE, pine bark extract.

Table 7B Overall efficacy rate after 18-month low-dose PBE administration (phase II, low-dose PBE trial)

Outcome
Markedly improved	1 (5)
Moderately improved	15 (71)
Slightly improved	5 (24)
Unchanged	0 (0)
Aggravated	0 (0)
Total	21

Note: Number of patients (%).

Abbreviation: PBE, pine bark extract.

Figure 3 The melanin index was significantly decreased after 4 and 12 weeks of oral administration of pine bark extract 100 mg/day.

Notes: The melanin index was calculated according to the method reported by Yamamoto et al.³¹ Values are expressed as the mean ± standard deviation. *P < 0.05 (Tukey–Kramer method), n = 24.

Figure 4 Time course of mean melanin index changes in age spots in group 1 (A) and group 2 (B).

Notes: A significant decrease in melanin index was seen after 4–8 weeks of oral pine bark extract 40 mg/day. Melanin index scores were calculated according to the method reported by Yamamoto et al.³¹ Values are expressed as the mean ± standard deviation. *P < 0.05 (Tukey–Kramer method), n = 38 (group 1), n = 39 (group 2).

Figure 5 Facultative skin color was assessed using a colorimeter followed by individual typology angle value calculation.

Notes: The Mann–Whitney U test was used to determine differences between baseline and after treatment with pine bark extract. There are no significant differences between baseline and following treatment with pine bark extract (P > 0.05), n = 21.
Abbreviation: ITA, individual typology angle.

Figure 6 Time course of corneocyte size changes measured by a planimetric method during pine bark extract administration.

Notes: The mean surface size of the corneocytes decreased significantly after 5 months of treatment with pine bark extract. Values are expressed as the mean ± standard deviation of corneocyte surface area. *P < 0.05 (unpaired t-test); **P < 0.05 (Mann–Whitney U test), n = 21.

Table 8A Results of hematology in 24 evaluated cases (high-dose PBE trial, 12-week administration)

Parameter (units)	Reference ranges	Baseline	12 weeks
Red blood cells (10^4/μL)	370–510	420.0 ± 31.2	420.2 ± 42.4
Hemoglobin (g/dL)	11–15.5	13.0 ± 0.7	12.8 ± 1.0
Hematocrit (%)	34–46	37.9 ± 2.9	38.1 ± 5.1
MCV (fL)	80–103	90.6 ± 6.1	90.9 ± 6.8a
MCH (pg)	26–35	30.6 ± 2.9	30.5 ± 3.3
MCHC (%)	31–36	33.7 ± 1.4	33.5 ± 1.5
Platelets (10^4/μL)	12–34	23.9 ± 5.7	24.8 ± 5.5
White blood cells (μL)	3500–9100	5276 ± 1780	5375 ± 1990
Neutrophil (%)	41–73	59.8 ± 9.3	60.5 ± 9.2
Lymphocyte (%)	20–50	32.0 ± 7.0	31.4 ± 7.5
Eosinophil (%)	0–9	2.3 ± 1.4	2.4 ± 1.5

Notes: Mean ± SD.

a P < 0.05, Student’s t-test for paired values, 2-tailed.

Abbreviations: PBE, pine bark extract. MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration.

Table 8B Results of hematology in 21 evaluated cases (phase II, low-dose PBE trial, 18-month administration)

Parameter (units)	Reference range	Group	Baseline	24 weeks	18 months
Red cell (10^4/μL)	370–510	I	434.1 ± 24.4	426.8 ± 32.4	428.7 ± 34.1
		II	422.7 ± 29.1	425.5 ± 23.3	425.5 ± 22.4
Hemoglobin (g/dL)	11–15.5	I	13.0 ± 0.7	12.8 ± 1.0	12.8 ± 1.1
		II	12.7 ± 0.7	13.0 ± 0.7	12.9 ± 0.7
Hematocrit (%)	34–46	I	40.6 ± 2.0	39.3 ± 2.9	39.7 ± 3.4
		II	40.7 ± 2.6	40.0 ± 2.1	40.5 ± 2.7
MCV (fL)	80–103	I	93.7 ± 4.5	92.2 ± 4.1	92.6 ± 4.8
		II	96.3 ± 2.5	94.1 ± 2.5	95.2 ± 4.5
MCH (pg)	26–35	I	30.1 ± 1.4	30.1 ± 1.5	29.9 ± 1.8
		II	30.0 ± 1.3	30.6 ± 1.1a	30.3 ± 0.9
MCHC (%)	31–36	I	32.2 ± 1.1	32.6 ± 1.3	32.3 ± 0.9
		II	31.2 ± 1.1	32.6 ± 0.5	31.9 ± 0.7
Platelet (10^4/μL)	12–34	I	27.5 ± 8.0	27.0 ± 5.3	27.3 ± 5.3
		II	26.4 ± 3.6	26.7 ± 3.8	26.4 ± 4.1
White cell (μL)	3500–9100	I	6193 ± 1876	6060 ± 1558	6253 ± 1799
		II	5883 ± 1222	5916 ± 1052	5283 ± 768
Neutrophil (%)	41–73	I	58.9 ± 6.9	58.7 ± 9.8	61.1 ± 10.3
		II	59.0 ± 7.1	59.2 ± 4.7	58.5 ± 4.5
Lymphocyte (%)	20–50	I	31.9 ± 5.7	32.8 ± 9.4	30.7 ± 9.6
		II	31.8 ± 5.9	32.2 ± 6.1	34.3 ± 2.4
Eosinophil (%)	0–9	I	3.3 ± 2.5	2.7 ± 1.8	2.9 ± 1.9
		II	3.8 ± 2.6	3.5 ± 2.5	2.7 ± 2.4

Notes: Mean ± SD.

a P < 0.01, Student’s t-test for paired values, 2-tailed.

Abbreviations: PBE, pine bark extract; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration.

Table 9A Results of blood chemistry in 24 evaluated cases (high dose PBE trial, 12-week administration)

Parameter (units)	Reference range	Baseline	12 weeks
Total cholesterol (mg/dL)	150–219	186.4 ± 39.2	185.1 ± 30.6a
HDL-C (mg/dL)	40–96	70.0 ± 14.3	63.1 ± 12.3
Triglycerides (mg/dL)	50–149	78.4 ± 40.1	82.3 ± 56.1
Aspartate aminotransferase (IU/l)	10–40	17.4 ± 3.0	16.6 ± 1.8
Alanine aminotransferase (IU/l)	5–40	13.9 ± 6.4	15.9 ± 8.3
Blood urea nitrogen (mg/dL)	6–20	11.7 ± 3.3	11.0 ± 2.8
Na^+ (mEq/l)	136–147	140.5 ± 1.7	139.1 ± 1.0b
K^+ (mEq/l)	3.6–5	4.2 ± 0.4	4.1 ± 0.4
Cl^− (mEq/l)	98–109	104.2 ± 1.9	103.5 ± 1.6a

Notes: Mean ± SD.

a P < 0.05,

b P < 0.01, Student’s t-test for paired values, 2-tailed.

Abbreviations: PBE, pine bark extract; HDL-C, high-density lipoprotein cholesterol.

Table 9B Results of blood chemistry in 21 evaluated cases (phase II, low-dose PBE trial, 18-month administration)

Parameter (units)	Reference range	Group	Baseline	24 weeks	18 months
Total cholesterol (mg/dL)	150–219	I	198.1 ± 33.2	192.9 ± 29.2	192.9 ± 32.5
		II	178.0 ± 36.0	171.5 ± 39.9	180.2 ± 40.3
HDL-C (mg/dL)	40–96	I	68.1 ± 15.8	65.9 ± 10.9	68.7 ± 14.6
		II	75.2 ± 11.4	72.2 ± 13.8	73.8 ± 14.2
LDL-C (mg/dL)	70–139	I	113.0 ± 23.8	113.1 ± 27.0	108.4 ± 23.3
		II	88.7 ± 35.9	89.8 ± 32.9	92.2 ± 28.4
Triglycerides (mg/dL)	50–149	I	87.9 ± 69.6	88.3 ± 41.0	82.3 ± 41.6
		II	54.5 ± 13.2	69.8 ± 37.0	58.5 ± 20.3
Free fat acid (mEq/l)	0.14–0.85	I	0.35 ± 0.18	0.39 ± 0.31	0.44 ± 0.34
		II	0.44 ± 0.22	0.32 ± 0.15	0.34 ± 0.26
Aspartate aminotransferase (IU/l)	10–40	I	19.3 ± 4.5	16.6 ± 1.8a	17.2 ± 3.6
		II	18.8 ± 2.4	19.5 ± 7.7	15.2 ± 2.2
Alanine aminotransferase (IU/l)	5–40	I	14.3 ± 6.8	11.3 ± 3.8	12.5 ± 4.8
		II	14.7 ± 4.4	16.2 ± 6.8	11.5 ± 2.7
Blood urea nitrogen (mg/dL)	6–20	I	12.6 ± 2.8	13.4 ± 4.2	13.2 ± 3.7
		II	12.8 ± 2.1	12.3 ± 1.3	12.1 ± 2.5
Na^+ (mEq/l)	136–147	I	139.9 ± 2.2	140.1 ± 1.2	139.5 ± 1.6
		II	138.7 ± 1.5	139.3 ± 1.8	139.7 ± 0.5
K^+ (mEq/l)	3.6–5	I	4.3 ± 0.7	4.3 ± 0.5	4.1 ± 0.6
		II	4.4 ± 0.5	4.3 ± 0.6	3.9 ± 0.3b
Cl^− (mEq/l)	98–109	I	104.0 ± 3.4	104.9 ± 1.8	104.6 ± 2.4
		II	103.8 ± 1.8	104.8 ± 2.0	104.3 ± 3.2
Iron (μg/dL)	48–154	I	81.5 ± 41.0	91.5 ± 40.1	86.9 ± 54.8
		II	84.0 ± 50.8	98.7 ± 19.0	88.8 ± 34.8
Ferritin (ng/mL)	7–110	I	20.2 ± 18.0	15.1 ± 18.7	19.5 ± 17.0
		II	29.5 ± 15.4	28.7 ± 15.7	33.4 ± 22.9

Notes: Mean ± SD.

a P < 0.05,

b P < 0.01, Student’s t-test for paired values, 2-tailed.

Abbreviations: PBE, pine bark extract; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol.

YamamotoTTakiwakiHAraseSOhshimaHDerivation and clinical application of special imaging by means of digital cameras and Image J freeware for quantification of erythema and pigmentationSkin Res Technol2008141263418211599

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