original article effects of health food containing ...2)0714.pdf · was to test the effectiveness...

7

IntroductionThe purpose of Anti-Aging Medicine is to promote daily

health and quality of life (QOL) and achieve a healthy long life for elderly people 1). In institutes practicing Anti-Aging Medicine, doctors evaluate aging and risk in individual patients and recommend appropriate Anti-Aging treatments.

Degeneration with aging is a phenomenon caused by a decrease in physiological function. This physiological dysfunction may cause various sicknesses and symptoms such as general fatigue, osteoporosis or cognitive dysfunction. As physiological functions deteriorate with age, the effectiveness of immune, endocrine and nervous systems begin to decrease and the impairment of immune function is especially marked in people over 60 years old 2). Therefore, it is important to strengthen an elderly person’s immunity to maintain health and promote QOL.

The herbal medicine Cistanche deserticola Y. C. Ma extract (CDX) (Koubakunikujuyou in Japanese) is reported to promote immune function 3). The purpose of the present study was to test the effectiveness and safety of orally administered health-food containing CDX in elderly persons. We report the results of a non-controlled open study with special reference to QOL and immune function.

Original Article

Effects of Health Food Containing Cistanche Deserticola Extract on QOL and Safety in Elderly: An Open Pilot Study of 12-week Oral Treatment

Yoshikazu Yonei 1), Takahiro Kitano 1), Mari Ogura 1), Mio Hori 1), Miwako Watanabe 2), Umenoi Hamada 1), Sayuri Matsuoka 3), Erika Ono 3), Tomohiro Ohno 3), Manzhen Shen 3)

1) Anti-Aging Medical Research Center, Graduate School of Life and Medical Sciences, Doshisha University2) Tokyo Midtown Medical Center 3) FANCL Research Institute, FANCL Corporation

AbstractObjective: The purpose of the present study was to elucidate the effects and safety of Cistanche deserticola Y. C. Ma extract (CDX), which was given to elderly persons as a 12-week oral administration via CDX containing health food.Methods: A non-controlled open study was conducted with 25 elderly persons, without severe illness. Participants were given test product containing 100 mg of CDX as well as vitamin E, vitamin B6, ubiquinone, zinc and fukoidan, by oral administration for 12 weeks, with examination conducted before and after the study.Results: Subjective symptoms of “tired eyes” and “feeling tired all the time” were significantly improved after 12 weeks. With regard to anthropometric measurements, pulse rate was significantly reduced (–8.0%, p = 0.002). Biochemical examinations showed significant changes in white blood cell count (–14.1%, p < 0.001), platelet count (–4.3%, p = 0.040), albumin (–3.7%, p < 0.001), albumin/globulin ratio (–3.7%, p = 0.016), and fasting blood sugar (–10.2%, p = .039). Immune function was significantly improved with elevation of percentage of CD4 positive cells (6.1%, p = 0.003), CD4/CD8 ratio (20.2%, p = 0.002) and natural killer (NK) cell activity (11.7%, p = 0.024) accompanied by a decrease in percentage of CD8 positive cells (–7.7%, p = 0.022). Arteriosclerosis examinations by fingertip acceleration pulse wave analysis showed significant improvement in vascular age (–4.2%, p = 0.016) and significant decrease in cardio ankle vascular index (CAVI) (right: –10.9%, p < 0.001, left: –12.6%, p <0.001).Conclusion: The test product appears to promote quality of life by decreasing fatigue, activating immune function and favorably affecting the vascular system in the elderly. No severe adverse effects were observed during the study.

KEY WORDS: Cistanche deserticola, immune function, CD4/CD8 ratio, NK cell, patient safety

Received:Nov. 30, 2010 Accepted:Feb. 14, 2011Published online:Apr. 8, 2011

Anti-Aging Medicine 8 (2) : 7-14, 2011(c) Japanese Society of Anti-Aging Medicine

Prof. Yoshikazu Yonei, M.D., Ph.D.Anti-Aging Medical Research Center, Graduate School of Life and Medical Sciences Doshisha University

1-3, Tatara Miyakodani, Kyotanabe city, Kyoto Prefecture, 610-0321 JAPANTel: +81-774-65-6382 / Fax: +81-774-65-6394 / E-mail: [email protected]

Methods

SubjectsThe subjects were 25 healthy volunteers age 65 to 80

years old (13 males and 12 females; mean age, 68.4 ± 3.5 years; body mass index [BMI], 22.7 ± 3.2 kg/m2) who did not meet the exclusion criteria listed below. All participants provided informed consent before joining the program and all 25 participants completed the program.

Exclusion criteria:(1) Those with severe diseases such as cardiovascular disease, hepatic and renal dysfunction, gastrointestinal disease, immune function disorder and cancer.(2) Those who took drugs or supplements containing coenzyme Q-10, vitamin E or zinc.(3) Those who constantly took drugs or supplements containing CDX (i.e. Yomei-shu).(4) Those who took Warfarin.(5) Those whom the investigators determined to be unsuitable for the study.

8

Effects of Cistanche deserticola Extract

Description of test productThe test product was provided by FANCL Corporation

(Yokohama-city, Kanagawa) as soft capsules. Each capsule contained CDX 16.7 mg (100 mg/day), vitamin E 33.3 mg (200 mg/day), coenzyme Q10 10 mg as ubiquinone (60 mg/day), vitamin B6 0.23 mg (1.4 mg/day), zinc 2.5 mg (15 mg/day) and sporophyll of Undaria pinnatifida extract (including Mekabu fucoidan) 1.7 mg (10 mg/day). Parentheses indicate the recommended daily amount in 6 capsules of each ingredient.

The principal ingredient of the test product is a dried powder extracted from C. deserticola Y. C. Ma with ethanol. It is regarded as an important herbal medicine for robustness and sexual energy reinforcement, recommended to individuals who feel worthless, experience nervous breakdown and feel general fatigue 3). The substance is not known to be genotoxic; no issues with animal safety were noted in the reverse mutation test or chromosomal aberration test (data provided by FANCL Corporation). A micronucleus test showed no abnormality at the highest dosage of 2500 mg/kg body weight, and the ferret emetic test showed no abnormality at the highest dose of 750 mg/kg body weight (data provided by FANCL Corporation). A repeated dose toxicity test over 90 days in SD rats found an increase in total cholesterol (TC), triglycerides (TG), total bilirubin in males, and the increase of blood urea nitrogen (BUN) and fasting plasma glucose (FPG) in females at high dose of 2500 mg/kg body weight, but no pathological issues were noted. A safe dosage is estimated to be 1250 mg/kg body-weight in both sexes (data provided by FANCL Corporation), which corresponds to 75 g/person/day assuming mean body-weight of 60 kg. This is about 750 times higher than the dosage used in the present study (100 mg/person/day).

Study designThe study was open-labeled and non-controlled. Participants

took a total of 6 soft capsules twice daily with water (3 capsules after breakfast and supper) for 12 weeks. Assessment of subjective symptoms, anthropometry, biochemical examination, immune function test, and arteriosclerosis examination were performed before and 12 weeks after the start of the study.

Participants were instructed to avoid excessive eating, demanding exercise, and lack of sleep and to continue the same alcohol consumption habits as before.

The subjects maintained a “daily diary” to record their health condition, any adverse effects, lifestyle-related habits, dietary and exercise condition, and compliance with instructions of the study product.

The study was completed between February 19 and May 14, 2010 at Mareesia Garden Clinic, Shinjuku-ku, Tokyo.

Evaluation methods

Subjective symptomsSubjective symptoms were divided into two categories,

physical and mental symptoms, and rated as described in our previous study 4) according to a 5-grade scale ranging from 1 to 5 points using the Anti-Aging QOL Common Questionnaire (AAQol).

AnthropometryThe following anthropometric parameters were recorded:

height (cm), body weight (kg), blood pressure (systolic/diastolic: mmHg), pulse rate (/min), and body composition using a body composition meter, BC118D (Tanita Corporation, Itabashi-ku, Tokyo) 4).

Biochemical examinationHematological parameters, including white blood cell

count (/μl), red blood cell count (×104/μl), hemoglobin (g/dl), hematocrit (%), platelet count (×104/μl), mean corpuscular volume (MCV) (fl), mean corpuscular hemoglobin (MCH) (pg), and mean corpuscular hemoglobin concentration (MCHC) (%); biochemical parameters, including total bilirubin (mg/dl), aspartate aminotransferase (AST) (IU/l), alanine transaminase (ALT) (IU/l), lactate dehydrogenase (LDH) (IU/l), alkaline phosphatase (ALP) (IU/l), γ-glutamyl transpeptidase (γ-GTP) (IU/l), creatine phosphokinase (CPK) (IU/l), uric acid (mg/dl), BUN (mg/dl), creatinine (mg/dl), for lipid and sugar metabolism, TC (mg/dl), high-density lipoprotein-cholesterol (HDL-C) (mg/dl), low-density lipoprotein-cholest rerol (LDL-C) (mg/dl), TG (mg/dl), atherogenic index , FPG (mg/dl), for protein metabolism, total protein (g/dl), albumin (g/dl), albumin /globulin (A/G) ratio, and for electrolytes, sodium (Na), potassium (K), chlorine (Cl) (mEq/l), calcium (Ca) (mg/dl), iron (Fe) (μg/dl), were determined. Biochemical measurements were completed at the Mitsubishi Chemical Medicine Corporation (Minato-ku, Tokyo). In addition, the atherogenic index (AI) was calculated from:

AI = (TC - HDL-C) ÷ HDL-C.

Immune functionThe number of CD4- and CD8-positive cells, CD4/CD8

ratio, and NK cell activity as reported previously 5) in the peripheral blood were measured to assess immune function at Mitsubishi Chemical Medicine.

Examination for arteriosclerosisArteriosclerosis indexes were determined by a VaSeraVS-100

(Fukuda Denshi, Bunkyo-ku, Tokyo) vascular screening system

4): cardio ankle vascular index (CAVI) and ankle brachial pressure index (ABI). While CAVI reflects vascular stiffness/tone 6,7), ABI is useful in assessing arterial stenosis/occlusion in the lower limbs 8). In addition, the fingertip acceleration pulse wave was determined using a plethysmometer (Dyna Pulse SDP-100, Fukuda Denshi) to calculate vascular age 9-11). In brief, second derivative of plethysmogram aging index (SDPTGAI) was calculated from parameters b/a, c/a, d/a, and e/a, and the vascular age (years old) was calculated by:

Male: vascular age = 43.50 x SDPTGAI + 65.90,Female: vascular age = 41.67 x SDPTGAI + 61.8.

Ethical ConsiderationsThe study was performed at a third party institution in

compliance with the ethical principles of the Declaration of Helsinki and the Personal Information Protection Law, and in accordance with “Ordinance regarding the Good Clinical Practice (GCP)” (MHW Ordinance No. 28 dated March 27, 1997). This study was approved by the ethical committee for clinical studies at Doshisha University and was conducted according to the standard approved protocol.

9


9

Statistical AnalysisResults are expressed as mean values ± standard deviation

(SD). Statistical analyses were performed using the statistical analysis software Stat.View Ver. 5 (SAS Institute Inc., Cary, North Carolina, USA) and Dr. SPSSII (SPSS Japan, Tokyo, Japan). Wilcoxon’s signed rank test for non-parametric data and a paired t-test for parametric data were used to compare measures before and after treatment. Results were considered significant at < 5% level. Patient safety was evaluated based on prevalence of adverse effects in the individual subjects.

Results

Subjective symptoms evaluated by the AAQolResults of subjective symptoms evaluated by the AAQol

are presented in Table 1. Of 32 physical symptoms, participants reported that two symptoms (“tired eyes” [p = 0.005] and “hair loss” [p = 0.022]) were significantly improved at Week 12. In additional questions about fatigue, the score for “feeling tired all the time” was significantly improved from 2.4 ± 1.0 to 2.0 ± 0.9 (p = 0.045) at Week 12. No significant improvements in 21 mental symptoms or lifestyle related behaviors were noted during the study (Table 2).

AnthropometryThere was no significant change in body composition or

blood pressure during the study (Table 3), although heart rate was significantly reduced (–8.0%, p = 0.002).

Table 1 Physical and mental symptoms

Week 0 Week 12 p value

Average ± SD, n = 25, Wilcoxon signed rank test.　* p < 0.05, ** p < 0.01.

2.9 2.8 1.5 3.0 2.8 1.7 1.8 2.9 1.4 2.0 1.8 2.0 1.9 1.5 1.7 1.5 1.8 1.7 1.5 2.1 2.5 4.0 1.7 1.4 1.4 2.1 2.2 1.5 2.2 2.3 1.8 2.1

2.5 2.4 1.7

1.7

1.6 1.8 1.9 1.9 1.7 1.7 1.6 1.7 1.6 1.6 2.3 2.0 1.9 2.9 2.2 1.9 1.7 1.9 2.0 1.7 1.5

±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±

±±±

±

±±±±±±±±±±±±±±±±±±±±±

1.0 1.1 0.6 1.2 1.2 0.9 1.0 1.3 0.6 0.9 1.0 0.8 0.8 0.8 0.8 0.7 0.7 0.7 0.7 1.2 1.0 0.9 0.8 0.6 0.8 1.1 1.0 0.7 1.1 1.2 1.0 1.1

1.0 1.0 0.8

0.9

0.6 0.8 1.0 0.9 0.9 0.9 0.9 0.8 0.7 0.6 1.2 1.1 0.8 1.2 1.1 1.0 0.7 0.8 0.8 0.7 0.6

2.4 2.6 1.5 2.7 2.7 1.5 1.7 2.9 1.4 2.0 1.8 2.2 1.8 1.5 1.6 1.4 1.8 1.8 1.6 2.0 2.0 3.7 1.7 1.5 1.5 2.0 2.0 1.4 2.2 2.1 1.7 2.0

2.2 2.0 1.6

1.6

1.6 1.7 2.0 1.8 1.6 1.8 1.2 1.4 1.4 1.6 2.1 1.8 1.6 2.7 2.0 1.6 1.6 1.8 1.8 1.6 1.3

±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±

±±±

±

±±±±±±±±±±±±±±±±±±±±±

1.0 1.1 0.8 1.3 1.2 0.8 0.9 1.2 0.7 1.0 0.8 0.8 0.7 0.7 0.6 0.8 0.8 0.9 0.8 1.2 0.7 1.1 0.8 0.8 1.0 1.2 1.0 0.6 1.2 1.1 0.9 0.9

0.9 0.9 0.8

0.8

0.7 0.7 0.8 0.9 0.9 0.9 0.9 0.9 0.6 0.9 1.3 1.1 0.6 0.9 0.8 0.6 0.6 0.9 0.7 0.7 0.5

0.005 0.166 0.851 0.153 0.808 0.305 0.615 0.806 0.405 0.782 0.813 0.334 0.467 0.666 0.564 0.593 >0.9990.589 0.822 0.564 0.022 0.205 0.813 0.366 0.180 0.516 0.138 0.317 0.675 0.197 0.509 0.635

0.132 0.045 0.527

0.813

>0.9990.366 0.271 0.655 0.257 0.248 0.132 0.071 0.248 >0.9990.308 0.153 0.106 0.446 0.379 0.088 0.317 0.467 0.439 0.516 0.248

**

*

*

Physical symptoms Tired eyes Blurry eyes Eye pain Stiff shoulders Muscular pain/stiffness Palpitations Shortness of breath Tendency to gain weight Weight loss; thin Lethargy Lack of sense of wellness Thirst Skin problems Anorexia Early satiety Epigastralgia Liable to catch colds Coughing and sputum Diarrhea Constipation Hair loss Gray hair Headache Dizziness Tinnitus Lumbago Arthralgia Edematous Easily breaking into a sweat Frequent urination Hot flashes Cold skin

Additional questions for fatigue Easy to become tired Feeling tired all the time Difficult to get up because it feels heavy in the morning Feeling heavy in the head

Mental symptoms Irritability Easily angered Loss of motivation No feeling of happiness Nothing to look forward to in life Daily life is not enjoyable Lose confidence Reluctance to talk with others Depressed Feeling of uselessness Shallow sleep Difficulty in falling asleep Pessimism Lapse of memory Inability to concentrate Inability to solve problems Inability to make judgments readily Inability to sleep because of worries A sense of tension Feeling of anxiety for no special reason Vague feeling of fear

Table 2 Lifestyle-related behaviors


Average ± SD, n = 25, Wilcoxon signed rank test.VDT; visual display terminal.

0.9 192 3.1

10.6 3.5 7.1 1.5 4.4

±±±±±±±±

3.5 237 2.8 16.1 2.6 1.2 0.7 1.8

0.9 245 3.0 9.7 3.4 7.0 1.4 4.1

±±±±±±±±

3.6 252 2.8 14.0 2.4 1.0 0.8 2.2

0.846 0.119 0.815 0.487 0.724 0.634 0.365 0.398

SmokingAlcohol consumptionFrequency of alcohol drinking Converted into ethanolExerciseSleeping hoursWater consumptionVDT working hours

Cigarettes/day ml/daytimes/weekml/daydays/weekhours/dayl/dayhours/day

Week 12 p value

8.2 11.4 7.6 5.6 8.5 6.3 239 3.2 19 14 13.5

58.2 26.7 15.7 42.5 31.1 1167 22.8 132

82 75.4

±±±±±±±±±±

11.8 7.7 5.6 9.0 6.6 252 3.3 19 14 10.3

0.382 0.199 0.197 0.938

- 0.884 0.477 0.663 0.892 0.002 **

Table 3 Anthropometry

Week 0

Average ± SD, n = 25, paired t-test.　** p < 0.01.BMI; body mass index.

159.3 58.0 26.4 15.5 42.5 31.1 1166 22.7 133

82 82.0

±±±±±±±±±±±

HeightWeightPercentage body fatAmount of fatLean body massWater contentBasal metabolic rateBMISystolic blood pressureDiastolic blood pressureHeart Rate

cmkg%kgkgkgkcal

mmHgmmHgbpm

10


Fig. 1. Immune function test

Biochemical examinationMeasures that were significantly changed by more than

± 3.0% during the study included WBC (–4.1%, p < 0.001), platelet (–4.3%, p = 0.040), Albumin (–3.7%, p < 0.001), A/G ratio (–3.7%, p = 0.016) and FPG (–10.2%, p = 0.039).

Immune functionThe percentage CD4-positive cells was signif icantly

increased (6.1%, p = 0.003), percentage and number of CD8-positive cells signif icantly decreased (–7.7%, p = 0.022, and –14.9%, p = 0.008, respectively), and CD4/CD8 ratio significantly increased (20.2%, p = 0.002) at Week 12 (Figure 1). NK cell activity significantly increased from the pre-value 54.0 ± 17.0% to 60.3 ± 16.4% (+11.7%, p = 0.024).

Examination for arteriosclerosisIn the fingertip acceleration pulse wave analysis, SDPTGAI

significantly decreased (p = 0.025) and the vascular age improved from 63.6 ± 8.0 to 61.0 ± 7.0 (–4.2%, p = 0.016) (Table 5). CAVI improved on both sides during the study (right: –10.9%, p < 0.001, left: –12.6%, p < 0.001). There was no significant change in ABI.

Table 4 Biochemical examination.


Average ± SD, n = 25, paired t-test.　* p<0.05, ** p<0.01.

6,116 440

13.5 43.2 24.0 98.5 30.7 31.2

7.6 4.5 1.5

25.0 24.6

205.6 0.1 0.7

216.0 52.2

113.6 15.3 0.84

5.7 142.9 103.7

4.1 9.7

96.4 230.1 132.2

67.8 118.8 93.9

2.5

±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±

1,51743 1.3 3.8 4.5 4.7 1.7 0.8 0.4 0.2 0.2 9.7 14.3 30.0 0.1 0.2 69.6 54.1 66.6 4.6 0.24 1.3 1.3 2.4 0.3 0.3 28.1 42.9 37.9 13.6 66.7 21.7 0.9

5,256439

13.4 42.8 23.0 97.4 30.7 31.4

7.4 4.3 1.4

24.8 22.7

201.6 0.1 0.8

205.1 53.5

110.4 15.2 0.85

5.7 141.9 102.1

4.1 9.6

107.6 224.5 130.8

65.8 127.6

84.4 2.5

±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±±

1,27441 1.3 3.6 5.1 4.4 2.1 1.0 0.4 0.2 0.2 12.8 11.5 31.0 0.1 0.3 54.3 64.6 43.1 4.3 0.24 1.2 1.8 2.2 0.5 0.3 34.7 45.6 42.3 15.1 102.0 8.6 0.9

<0.0010.871 0.779 0.184 0.040 0.005 0.973 0.145 0.021 0.000 0.016 0.913 0.287 0.351 0.664 0.009 0.052 0.672 0.722 0.784 0.514 0.818 0.008 <0.0010.810 0.236 0.075 0.198 0.680 0.251 0.475 0.039 0.702

**

***

****

****

*

White blood cellRed blood cellHemoglobinHematocritPlateletMCVMCHMCHCTotal proteinAlbuminA/G ratioASTALTLDHDirect bilirubinIndirect bilirubinALPγ-GTPCPKBUNCreatinineUric acidNaClKCaFeTCLDL-CHDL-CTGFPGAtherogenic index

/μl×104/μl

g/dl%

×104/μlflpg%

g/dlg/dl-

IU/l/37°CIU/l/37°CIU/l/37°C

mg/dlmg/dl

IU/l/37°CIU/l/37°CIU/l/37°C

mg/dlmg/dlmg/dlmEq/lmEq/lmEq/lmg/dlμg/dlmg/dlmg/dlmg/dlmg/dlmg/dl-

MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; A/G ratio, albumin/globlin ratio; AST, aspartate aminotransferase; ALT, alanine transaminase; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; γ-GTP, γ-glutamyl transpeptidase; CPK, creatine phosphokinase; BUN, blood urea nitrogen; Na, sodium; Cl, chlorine; K, potassium; Ca, calcium; Fe, iron; TC, total cholesterol; LDL-C, low density lipoprotein-cholesterol; HDL-C, high density lipoprotein-cholesterol; TG, triglyceride; FPG, fasting plasma glucose.

Week 12 p value

8.0 0.20 0.15 0.15 0.11 0.06 14 18 31 30 117 0.15

0.8 1.1 0.10 0.14

61.0 –0.05 –0.48 –0.20 –0.36

0.14 94

145 190 283 826

1.15

8.4 8.3

1.13 1.13

±±±±±±±±±±±±

±±±±

7.0 0.17 0.12 0.13 0.11 0.06 23 25 40 28 105 0.12

1.1 1.1 0.11 0.13

0.016 0.025 0.468 0.275 0.068 0.746 0.419 0.292 0.576 0.292 0.102 0.430

<0.001<0.0010.313 0.379

**

****

Table 5 Examination for arteriosclerosis

Week 0

Average ± SD, n = 25, paired t-test.* p < 0.05, ** p < 0.01.SDPTGAI, second derivative of plethysmogram aging index.PTGAI, plethysmogram aging index.CAVI, cardio ankle vascular index; ABI, ankle brachial pressure index.

63.6 0.00

–0.50 –0.23 –0.41

0.13 91

151 195 289 796

1.17

9.4 9.4

1.16 1.15

±±±±±±±±±±±±

±±±±

Finger tip acceleration pulse wave analysisVascular ageSDPTGAI

b/ac/ad/ae/ab-ac-ad-ae-aa-a

PTGAICAVI

CAVI (right) (left)

ABI (right) (left)

years－－－－－msmsmsmsms－

－－－－

11


11

Table 6 Profile of cases with abnormal values in the biochemical examination

ItemAgeSexID Standardvalues

105

506530

-----

4045200139149

5040

14487

248

2 M 66

3 M 68

ASTALTFe

LDL-CTG

Week 0February 19th May 14th

8053

20744

482

60.0 32.5 43.8

–49.4 94.4

– 0.8 –7.5 11.7 –1.1

7.4

↑ ↑ ↑↓ ↑

120 - 240 232LDH 278 19.8 –2.0 ↑

5 F 66 3.5 - 5.0 4.1K 5.2 26.8 0.6 ↑

9 F 71

8 M 68

5 - 45 44ALT 46 4.5 –7.5 ↑

14 F 70 2.5 - 7.0 6.1Uric acid 7.2 18.0 –0.6 ↑

20 M 66 98 - 108 100Cl 97 –3.0 –1.5↓

21 M 66 3.8 - 7.0 6.5Uric acid 7.1 9.2 –0.6 ↑

10 M 65 40 - 85 43HDL-C 36 –16.3 –2.9↓

Week 12 Up ordown

% change (%)

Effectsize Comment Judgment

He drank alcohol on May 13th.

No correlation with the test product due to alcohol intake.

43013.539.7

8.050

-----

57017.552.420.0200

45212.242.119.1

51

7 M 75

RBCHemoglobinHematocrit

BUNFe

42411.238.724.3

49

–6.2–8.2–8.127.2–3.9

–0.1–0.2–1.1–0.911.7

↓↓↓ ↑↓

12065

--

219139

219131

TCLDL-C

230145

5.010.7

–2.4–1.1

↑ ↑

28.06.7

--

34.08.3

28.58.2

MCHTotal protein

27.68.5

–3.23.7

0.0–2.0

↓ ↑

Currently being treated for chronic heart failure.

No correlation with the test product due to the present illness.

0.230

12065

-----

1.0149219139

0.8131303197

25 F 72

Indirect bilirubinTGTC

LDL-C

1.1226342229

37.572.512.916.2

10.47.4

–2.4–1.1

↑ ↑ ↑ ↑

Diagnosed as dyslipidemia, but receives no medical treatment.

No correlation with the test product due to food intake and illness (dyslipidemia).

14.0120

65

---

34.0219139

33.5217119

11 F 69Platelet

TCLDL-C

35.7231140

6.66.5

17.6

–4.3–2.4–1.1

↑ ↑ ↑

She caught common cold 3 times during the study.

No correlation with the test product due to food intake and prevalence of common cold.

28.01000.2

---

34.03251.0

33.31291.2

17

19

M 69MCHALP

Indirect bilirubin

34.380

1.5

3.0–38.0

25.0

0.0–5.010.4

↑↓ ↑

RBC was low and MCV was high during the study.

Low correlation with the test product. The cause remains unclear.

Currently being treated for hypertension and prostatic gland hypertrophy at present with elevated BUN and creatinine.

No correlation with the test product due to food intake and illness.

3.5

65

-

-

5.0

139

3.8

133M 65

K

LDL-C

3.1

146

–18.4

9.8

0.6

–1.1

↓

↑

Low correlation with the test product. Both increased and decreased K were noted and judged due to food intake.

No correlation with the test product due to food intake.

Low correlation with the test product. The cause is unclear.

23 M 66 0.2 - 1.0 1.3Indirect bilirubin 1.6 23.1 10.4 ↑ Low correlation with the test product, the cause is unclear.

24 F 67No correlation with the test product, due to food intake.

Currently being treated for liver dysfunction, elevated ALP and γ-GTP.

No correlation with the test product due to the present illness.

Low correlation with the test product, the cause is unclear.

No correlation with the test product due to food intake.

Currently being treated for gout and renal dysfunction.

No correlation with the test product due to the diagnosed illness.

Increased and decreased K were noted in the study and judged due to food intake. Low correlation with the test product.

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Patient safetyProfiles of 16 cases in which biochemical examinations

showed slightly abnormal change are presented in Table 6. Items which showed abnormal values were peripheral blood (RBC, Hb, Ht, platelet and MCH) in 4 cases, liver function (AST, ALT, LDH, ALP and indirect bilirubin) in 6 cases, renal function (BUN and uric acid) in 3 cases, lipid profile (TC, LDL-C and HDL-C) in 6 cases, protein metabolism (total protein) in 1 case and electrolytes (K, Cl and Fe) in 5 cases. Of these 16 cases, 5 participants reported slight disease including gout, renal dysfunction, congestive heart failure, liver dysfunction, hypertension or dyslipidemia and one participant caught cold (upper respiratory viral infection) during the study. Abnormal changes of AST and ALT were associated with alcohol intake. Abnormal changes in lipid profile were caused by inadequate food intake. The reasons for changes in indirect bilirubin, HDL-C, ALP and Cl have not been identified, but we consider it unlikely the test product was responsible. No severe adverse effect was observed during and after the study.

Discussion

Significance of the present studyMany age related symptoms such as tiredness, osteoporosis,

and dementia can be traced to decreases in physiology function. For example, immune response declines sharply over age 60 as the immunological system, the internal secretion system and the nervous system all weaken 2). If immunity can be strengthened, then QOL and health of the aged will be improved.

Here we examined foods containing CDX which have been reported to improve immunity and QOL among senior citizens

3). Other components of the capsules include fucoidans 12,13), vitamin E 14-16), zinc 17,18), vitamin B6 and coenzyme Q10 19). These supplements have been used in traditional Chinese medicine as nutritional fortification elements and are believed to improve immune function.

Improvement in immune function, arising from improved physiology function, is thought to improve QOL among senior citizens. The present study was a pilot trial to verify whether human immune function, subjective symptoms and QOL, especially in persons of advanced years, were improved by taking the CDX.

About C. deserticola extractThe principal ingredient in CDX is phenylethyanoid, which

is reported to have antioxidant action 20), liver propagation action 21-23), and T-cell proliferation action 24). Moreover, polysaccharides from CDX have immunostimulatory activity, such as promoting T-cell and B cell proliferation 25-27).

Tests of CDX in mice demonstrated improved immune function 28), swimming capacity, and endurance 29,30). Sedative action has been reported 31) in rats, and laboratory models of rodents 32) have shown analgesic action and anti-inflammation activity. Pregnancy rate in mice fed Tripterygium wilfordii was improved 33). Aging mice treated with phenylethyanoid showed improvements in D-galactose levels, which affect learning ability and memory; reinforcement of superoxide dismutase (SOD) in blood serum and brain tissue; reduction in malondialdehyde (MDA) in blood serum and liver; and

improved function of the spleen and thymus 34).In the present study, CDX had various effects in addition to

immunostimulatory activity. However, this is the first clinical trial of this substance.

Data analysisThe AAQol subjective physical symptoms “tired eyes”

and “hair loss” “feeling tired all the time” symptoms were significantly improved. The anti-fatigue effects of CDX have been confirmed in previous studies 29,30), and we suggest that the relief of “tired eyes” and “feeling tired all the time” were related although the relationship of anti-fatigue effects to “hair loss” could not be clarified.

Examination of peripheral blood indicated a significant decrease in white blood cell counts within the normal range. CDX has been reported to exert anti-inflammatory effects 32), and this suggests the extract may have reduced inflammatory cytokine response, consequently decreasing white blood cell counts. Among inf lammatory cytokines, IL6 is known to increase platelet counts 35), and any decrease in IL6 leads to a decrease in platelet counts.

Zinc contained in the test product is thought to be the primary cause of reduced blood sugar levels observed in this study. Zinc is an essential mineral for the synthesis and secretion of insulin, and zinc deficiency leads to a decrease in insulin secretion and increase in blood sugar levels 36). Cases of insufficient zinc intake are especially common among those over 65 years of age 17,18), and thus the effects noted in this study may arise from zinc supplements.

We were unable to clarify the mechanism for the significant decrease in albumin and A/G ratios. The decreases observed in both values were within the normal range (approximately 3.7% decrease) and were judged to be a physiological variation.

T-cells were divided into subsets according to their function. Among these subsets, CD4-positive cells act on B-cells and induce immunoglobulin synthesis, whereas CD8-positive cells have an inhibitory effect. In immunodeficiency diseases and lymphatic malignancies, the ratio of CD4-positive cells to CD8-positive cells (CD4/CD8 ratio) decreases. This ratio is a useful index for the diagnosis and treatment for such diseases. In this study, percentage of CD4-positive cells showed a significant increase, while the percentage of CD8-positive cells showed a significant decrease, thereby confirming a significant increase in the CD4/CD8 ratio. The increased value of CD4/CD8 ratio indicates the activation of immune function.

NK cells play an important role in the early defense mechanism. NK cell activity decreases starting from about 40 years of age, and decreases further under added stress. The decrease in NK cell activity leads to reduced resistance, making the body more susceptible to viral infection 37). The significant increase in NK cell activity observed in this study indicates the activation of the immune function.

With regard to arteriosclerosis, measurements of fingertip acceleration pulse waves showed significant improvements in vascular age and CAVI values decreased significantly. These tests reflect both organic hardening and tension of the vascular wall. Because organic improvements are difficult to obtain in an observation period of only 12 weeks, we conclude that the improvements observed were primarily due to reduced tensions. Vascular tension ref lects the balance between endothelial cell-derived nitric oxide (NO) and NO-derived free radicals.

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In general, antioxidants exert vasodilator effects, while free radicals exert vasoconstrictor effects and add vascular tension 38). Test products used here contain CDX extract 20,34), vitamin E 14-16), and coenzyme Q10 19), all of which have antioxidant effects. These ingredients may have acted as vasodilators, thereby reducing vascular tension. As a result, cardiac stress was reduced and led to the significant decrease in heart rate.

A key limitation of this study is that the test product contained additional functional ingredients other than CDX including vitamin E, coenzyme Q10, vitamin B6, zinc and sporophyll of Undaria pinnatifida extract. Thus, the results observed cannot be assigned solely to CDX extract. In addition, the observation period of this study was 12 weeks. A long term observation of more than 3 years may provide further information regarding effectiveness and patient safety.

Patient safetyParticipants in the study were aged >65 years, and many

had lifestyle-related diseases. Some participants may have had slight chronic cardiac insufficiency. Blood biochemical tests are highly influenced by alcohol or water intake and dehydration. We identified 16 anomalous results during the study, but we judge these findings to have little or no effect on the trial.

No serious harmful effects were recognized during the trial, and therefore we judged the test compounds to be safe for use. But we judged that every case of them was a little relation to trial samples. However, when elderly individuals with underlying disease ingest test samples, they should inform their doctor and undergo blood biochemistry tests once every three or four months.

1) Yonei Y, Takahashi Y, Hibino S: Senile degeneration and the future prospects of Anti-Aging Medicine. Nippon Rinsho 67:1256-1260, 2009 (in Japanese)

2) Hirokawa K, Utsuyama M: Animal models and possible human application of immunological restoration in the elderly. Mech Ageing Dev 123:1055-1063, 2002

3) Jin XL, Zhang QR: Recent progress in the study on chemical constituents of herba Cistanche. Zhongguo Zhong Yao Za Zhi 19:695-697, 704, 1994 (in Chinese)

4) Iwabayashi M, Fujioka N, Nomoto K, et al: Efficacy and safety of eight-week treatment with astaxanthin in individuals screened for increased oxidative stress burden. Anti-Aging Medicine 6:15-21, 2009

5) Yonei Y, Takahashi Y, Matsushita K, et al: Double blind study of health claims for food containing extract of Kabanoanatake

(Charga: Fuscoporia obliqua) (RCT: randomized controlled trial). Anti-Aging Medicine 4:1-10, 2007

6) Shirai K, Utino J, Otsuka K, et al: A novel blood pressure-independent arterial wall stiffness parameter: Cardio-Ankle Vascular Index (CAVI). J Atherosclerosis and Thrombosis 13:101-107, 2006

7) Kubozono T, Miyata M, Ueyama K, et al: Clinical significance and reproducibility of new ar ter ial distensibility index. Circulation Journal 71:89-94, 2006

8) Ankle Brachial Index Collaboration Group. Fowkes FG, Murray GD, Butcher I, et al: Ankle brachial index combined with

ConclusionsA non-control open study of 25 elderly participants without

severe illness was conducted to elucidate the effect and safety of 12-week oral administration of health food containing CDX. This is reported to promote immune function. Subjective symptoms of “tired eyes” and “feeling tired all the time” were significantly improved. Measures of immune function, arteriosclerosis and vascular age were significantly improved. No severe adverse effects were caused by the test product. These findings suggest that the test product may promote QOL by decreasing feelings of fatigue, activating immune function and favorably affecting the vascular system among the elderly.

Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA 300:197-208, 2008

9) Takada H, Okino K, Niwa Y: An evaluation method for heart rate variability by using acceleration plethysmography. Health Evaluation & Promotion (Sogokenshin) 31:547-551, 2004

10) Ushiroyama T, Kajimoto Y, Sakuma K, et al: Assessment of chilly sensation in Japanese women with laser doppler fluxmetry and acceleration plethysmogram with respect to peripheral circulation. Bulletin of the Osaka Medical College 51:76-84, 2005

11) Takazawa K, Kobayashi H, Shindo N, et al: Relationship between radial and central arterial pulse wave and evaluation of central aortic pressure using the radial arterial pulse wave. Hypertens Res 30:219-228, 2007

12) Aisa Y, Miyakawa Y, Nakazato T, et al: Fucoidan induces apoptosis of human HS-sultan cells accompanied by activation of caspase-3 and down-regulation of ERK pathways. Am J Hematol 78:7-14, 2005

13) Fujioka N, Hibino S, Wakahara A, et al: Effects of various soap elements on skin. Anti-Aging Medicine 6: 109-118, 2009.

14) Meydani SN, Meydani M, Blumberg JB, et al: Vitamin E supplementation and in vivo immune response in healthy elderly subjects. JAMA 277:1380-1386, 1997

15) Meydani SN, Leka LS, Fine BC, et al: Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA 292:828-836, 2004

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