Effects of Astaxanthin on Liver and Leukocyte Parameters in Healthy Climacteric Women: Preliminary Data

Abstract

Astaxanthin, a xanthophyll carotenoid and a cell-protective micronutrient (i.e., with antioxidative action), is often used as a dietary supplement among health conscious people. Although astaxanthin is well known to have an antioxidative function, there are also other health benefits (i.e., anti-inflammation, immunomodulation) that are well documented.^1,2 Thus, the effects of astaxanthin supplementation on health should be further examined; however, there is currently a paucity of data obtained from clinical studies in an evidence-based manner among relatively healthy people. This study aimed to observe the changes in laboratory measures following astaxanthin supplementation among healthy climacteric women (this population generally uses supplementations including astaxanthin).

The study was a double-blinded randomized controlled clinical trial (approved by the institute Ethical Committee, UMIN trial No. 000011834) on astaxanthin supplementation for healthy women. Informed consent was obtained from the participants. Inclusion criteria were subjectively healthy women in a climacteric phase. Histories of hormone replacement therapy, current smoking habits, cardiometabolic diseases, and the use of antioxidant supplements comprised the exclusion criteria. Finally, 14 women were administered 12 mg/day astaxanthin, while 15 women received a placebo over a period of 3 months. Their respective laboratory measures were determined during a fast before and after treatment. The examinations of blood samples were conducted in a single center of a nationally certified laboratory (LSI Co. Ltd., Tokyo, Japan). As oxidative stress markers, the levels of blood diacron-reactive oxygen metabolites (d-ROMs)³ and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) were determined, while as an antioxidative marker, the levels of biological antioxidant potential (BAP) were determined.⁴

The results of laboratory measures are summarized in Table 1. There was a significant decrease in the levels of serum liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransaminase (ALT), in astaxanthin-treated women. No significant changes were observed in the levels of serum d-ROMs and urinary 8-OHdG in addition to the levels of BAP following astaxanthin treatment. A significant increase in blood leukocytes was also found in astaxanthin-treated women.

Table 1.

Changes in Physical and Biochemical Parameters Following Astaxanthin Supplementation for 3 Months

	Placebo (n = 15)		Astaxanthin, 12 mg/day (n = 14)
	Pre	Post	Pre	Post	P
Age, years	52 ± 4	—	51 ± 5	—	.49
BMI, kg/m²	21.9 ± 4.6	21.5 ± 4.6	21.3 ± 2.7	21.5 ± 2.7	.81
Systolic BP, mmHg	125 ± 25	121 ± 22	123 ± 16	124 ± 14	.97
Diastolic BP, mmHg	80 ± 15	79 ± 11	83 ± 11	80 ± 11	.65
Leukocyte, count/μL	5493 ± 927	5613 ± 1287	4493 ± 1059	4793 ± 1296	.03^a
Neutrophil, count/μL	3051 ± 835	3308 ± 808	2608 ± 798	2782 ± 960	.10
Lymphocyte, count/μL	1974 ± 565	1862 ± 774	1450 ± 270	1572 ± 373	.03^a
AST, U/L	23 (19–25)	23 (18–27)	21 (16–23)	17 (14–25)	.046^a
ALT, U/L	21 (16–32)	19 (14–26)	15 (14–20)	15 (11–18)	.03^a
γ-GT, U/L	19 (14–26)	20 (12–37)	16 (14–22)	15 (11–23)	.30
Cre, mg/dL	.65 ± 0.07	.64 ± 0.07	.64 ± 0.09	.62 ± 0.08	.63
LDL-C, mg/dL	124 ± 32	120 ± 21	133 ± 27	120 ± 25	.58
HDL-C, mg/dL	76 ± 16	77 ± 17	72 ± 14	72 ± 13	.39
TG, mg/dL	96 (62–138)	96 (70–127)	92 (76–143)	121 (83–143)	.61
Fibrinogen, mg/dL	268 ± 37	267 ± 38	259 ± 33	262 ± 56	.79
hsCRP, mg/dL	.02 (.01–.07)	.04 (.01–.11)	.03 (.01–.04)	.02 (.01–.03)	.31
FSH, mU/mL	60.5 (36.0–64.0)	58.2 (22.0–77.8)	60.6 (45.5–95.4)	43.1 (28.9–94.0)	.90
E₂, pg/mL	20.2 (10.0–26.9)	19.7 (11.8–51.7)	11.0 (10.0–29.1)	41.2 (11.5–70.5)	.83
d-ROMs, Carr U	368 ± 49	354 ± 100	366 ± 46	365 ± 73	.84
BAP, μU	1887 ± 107	2024 ± 207	1921 ± 93	1939 ± 86	.49
8-OHdG/Cre, ng/mg Cre	5.4 (4.6–6.5)	5.3 (4.4–8.2)	6.6 (6.1–8.9)	5.8 (4.3–8.9)	.26

Data is provided as mean ± standard deviation or median (interquartile range). Comparison between pre- and post-data was performed using two-way repeated measures ANOVA (skewed data were used after log-transformations for the normal distributions).

P < .05.

8-OHdG, 8- hydroxy-2′-deoxyguanosine; ALT, alanine transaminase; AST, aspartate aminotransferase; BAP, biological antioxidant potential; BMI: body mass index, BP: blood pressure, Cre, creatinine; d-ROMs, diacron-reactive oxygen metabolites; E₂, estradiol; FSH, follicular stimulating hormone; HDL, high-density lipoprotein; hsCRP, high-sensitivity C-reactive protein; LDL, low-density lipoprotein; TG, triglyceride; γ-GT, γ-glutamyltransferase.

In the current exploratory study on healthy climacteric women, the slight but significant reduction in the levels of ALT and AST during astaxanthin supplementation is of interest. An earlier study (only one human clinical study that has previously examined the effects of astaxanthin on the liver) reported histopathological improvements of liver tissues in patients with nonalcoholic steatohepatitis following 6 months of astaxanthin treatment.⁵ Even though the levels of liver enzymes in our current study remained within a normal range, and we must be careful to determine the clinical relevance of such results, they could be reflective of a potential liver protective effect of astaxanthin, because a normal level of blood liver enzymes is frequently observed in people with liver pathologies (in which oxidative stress is partly involved).^5,6 Considering that liver pathologies are a target of the prevention of future cardiometabolic and cancerous disorders,^5,6 the relevance of the potential liver protection by astaxanthin may be important. In this study, the changes in the levels of liver enzymes were not accompanied by any significant changes in the blood/urinary oxidative stress and antioxidative markers. One possible explanation for these results is that astaxanthin possesses an independent antioxidative action; for example, via an alleviated insulin resistance in liver tissues.⁷ Alternatively, because astaxanthin accumulates and has functional bioactivities within liver tissues,⁸ it is also possible that astaxanthin exerts a direct antioxidative effect that is not being expressed in the blood oxidative stress and antioxidative markers. To clarify the explanations in our present study and the difference in results between ours and the earlier study [describing no changes in the levels of blood liver enzymes (AST = 48 and ALT = 70 U/L: high levels relative to this study) during an astaxanthin treatment period],⁵ further studies are necessary.

In addition, the significant increase in blood leukocytes following astaxanthin supplementation was unexpected in this study. Astaxanthin is known to modulate the immune system,¹ but whether the leukocytes change via the modulation remains unclear. This is a new phenomenon and may merit further investigations.

This study had some limitations. There were limited numbers of study subjects and the study was conducted over a short duration. Liver pathologies were not fully evaluated, for instance, using ultrasonic and/or histopathological methods. The impacts of liver and leukocyte data as influenced by astaxanthin supplementation on clinical outcomes remain undetermined.

In summary, astaxanthin supplementation can be considered to have a protective effect on the liver even in subjectively healthy climacteric women. Astaxanthin may also modulate the levels of blood leukocytes, but this remains subject to further investigation. Since there have been limited human clinical studies in a sophisticated manner, more data from such studies are required for definite conclusions.

Footnotes

Author Disclosure Statement

J.T.C received a lecture fee from the Fuji-Kagaku Co. Ltd., Japan.

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