Re:히스타민 증후군의 비타민, 미네랄, 영양치료법, SAMe구입과 복용법

[문형철]

BEYOND REASON

어떤 사람에게 좋은 음식이 어떤 사람에게는 독이 된다

히스타민을 분비하는 세포막 안정화하기

- 히스타민은 히스타민을 분비하는 세포(ex, mast cell)에서 탈과립되면서 분비됨. 그러므로 히스타민을 분비하는 비만세포의 막을 안정화하면 히스타민 분비를 억제할 수 있음. 

- 대표적인 식품이 '양파의 성분이 케르세틴'과 '민들레, 들께, 브로콜리, 피망, 파슬리에 함유된 루테올린'임. 

- 참고로 항히스타민제는 졸림 등의 부작용이 있음

  그리고 염증성 물질인 '세로토닌, 프로스타글란딘, 사이토카인' 등 다양한 물질을 다 억제하지는 못함. 

히스타민 증후군의 비약물적 영양치료

1) 다래 추출물

- 국내 최초 면역과민반응 개선기능에 대한 개별인정을 획독한 제품

2) 브로멜레인

- 브로멜레인은 파인애플에서 추출한 단백분해효소(sulfhydryl proteolytic enzyme)임. 

- 1957년부터 소개된 아주 오래도니 제제임. 

- 브로멜레인의 효과는 혈소판응집을 억제하고 섬유소를 용해하고 항염 특히 히스타민 분비를 촉진하는 브라디키닌 작용을 억제함. 

Biotechnol Res Int. 2012; 2012: 976203. 

Published online 2012 Dec 10. doi: 10.1155/2012/976203

PMCID: PMC3529416

PMID: 23304525

Properties and Therapeutic Application of Bromelain: A Review

Rajendra Pavan, Sapna Jain, Shraddha, and  Ajay Kumar*

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Abstract

Bromelain belongs to a group of protein digesting enzymes obtained commercially from the fruit or stem of pineapple. Fruit bromelain and stem bromelainare prepared differently and they contain different enzymatic composition. “Bromelain” refers usually to the “stem bromelain.” Bromelain is a mixture of different thiol endopeptidases and other components like phosphatase, glucosidase, peroxidase, cellulase, escharase, and several protease inhibitors. In vitro and in vivo studies demonstrate that bromelain exhibits various fibrinolytic, antiedematous, antithrombotic, and anti-inflammatory activities. Bromelain is considerably absorbable in the body without losing its proteolytic activity and without producing any major side effects. Bromelain accounts for many therapeutic benefits like the treatment of angina pectoris, bronchitis, sinusitis, surgical trauma, and thrombophlebitis, debridement of wounds, and enhanced absorption of drugs, particularly antibiotics. It also relieves osteoarthritis, diarrhea, and various cardiovascular disorders. Bromelain also possesses some anticancerous activities and promotes apoptotic cell death. This paper reviews the important properties and therapeutic applications of bromelain, along with the possible mode of action.

Bromelain: Methods of Extraction, Purification and Therapeutic Applications

Zoya Manzoor1 

Ali Nawaz1  * 

Hamid Mukhtar1 

Ikram Haq¹ 

¹Institute of Industrial Biotechnology GC University Lahore, Pakistan

---

ABSTRACT

Bromelain is a concoction of sulfhydryl proteolytic enzymes. Depending upon the site of extraction it can be regarded as either stem bromelain (SBM) (EC 3.4.22.32) or fruit bromelain (FBM) (EC 3.4.22.33). Bromelain remain enzymatic active over a broad spectrumand endure a range of pH (5.5 to 8.0) and temperature (35.5 to 71 ºC). It is one of the extensively investigated proteolytic enzyme owing to its astonishing applications in various industries. This necessitated employing a strategy that result in highest purified bromelain in less steps and lowest cost. Use of modernistic approach such as membrane filtration, reverse micellar systems, aqueous two phase extraction and chromatographic techniques have shown promise in this regard. Besides its industrial applications, bromelain has been widely utilized as a potential phytomedical compound. Some of its reported actions include inhibition of platelet aggregation, anti-edematous, anti-thrombotic, anti-inflammatory, modulation of cytokines and immunity, skin debridement and fibrinolytic activity. It also assist digestion, enhance absorption of other drugs and is a potential postoperatively agent that promote wound healing and reduce postsurgical discomfort and swelling.

3) 테아닌(Theanine)

- 테아닌은 차와 일부 버섯에 있는 천연 유리 아미노산으로 특히 홍차, 녹차에 많음. 

- 테아닌은 녹차 특유의 아미노산으로 이것의 함량은 차에 함유된 총 아미노산의 약 50%에 달하고 녹차말린 잎 중량의 1-2%차지. 테아닌은 BBB를 통과하여 이완시키는 효과가 있음. 이는 테아닌이 뇌신경세포에서 신경전달물질 방출에 영향을 미침. 즉 GABA수치를 올려 과도한 흥분을 억제하고 세로토닌, 도파민을 증가시킴. 만성통증에 관여하는 AMPA(alpha-amino-3-hydorxy-5-methyl-4-isoxazolepropionic acid) 수용체, 카이닌산 수용체와 NMDA수용체 대항작용을 함. 

- 테아닌은 글루타민 glutamic acid의 과도한 자극을 억제하여 뇌에서 안정감을 주는 알파파를 증진함. 

- 특히 Th2세포 작용을 억제해 과민면역반응을 억제하는 작용을 하기 때문에 뇌와 관련된 히스타민 증후군 치료에 응용가능함. 

Green tea and theanine: health benefits

RAYMOND COOPER

Stratum Nutrition, Novus International, 20 Research Park Drive, St. Charles, MO, USA and Hong Kong Polytechnic University, Hong Kong

( Received 31 August 2011; revised 29 September 2011; accepted 30 September 2011 )

Abstract

Historically, the medicinal use of green tea dates back to China 4700 years ago and drinking tea continues to be regarded traditionally in Asia as a general healthful practice. Numerous scientific publications now attest to the health benefits of both black and green teas, including clinical and epidemiological studies. Although all tea contains beneficial antioxidants, high-quality green and white teas have them in greater concentrations than black tea. Today, scientists believe that the main active ingredients of green tea include the polyphenols, in particular the catechins and the amino acid, theanine. Studies on the health benefits of drinking tea, particularly green tea, are finding exciting results, particularly in cancer research. Modern studies in both Asia and the West have provided encouraging results indicating that drinking green tea contributes to fighting many different kinds of cancers including stomach, oesophageal, ovarian and colon. Recent studies describing the health benefits of these compounds will be reviewed. 

Acta Neuropsychiatr. 2017 Apr;29(2):72-79. doi: 10.1017/neu.2016.33. Epub 2016 Jul 11.

Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study.

Hidese S1, Ota M1, Wakabayashi C1, Noda T2, Ozawa H3, Okubo T3, Kunugi H1.

Author information

1

1Department of Mental Disorder Research,National Institute of Neuroscience,National Center of Neurology and Psychiatry,Tokyo,Japan.

2

3Department of Psychiatry,National Center Hospital,National Center of Neurology and Psychiatry,Tokyo,Japan.

3

4Department of Research and Development,Nutrition Division,Taiyo Kagaku Co. Ltd,Mie,Japan.

Abstract

OBJECTIVE: 

l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial.

METHODS: 

Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS).

RESULTS: 

HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration.

CONCLUSION: 

Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.

Amino Acids. 2012 May;42(5):1609-18. doi: 10.1007/s00726-011-0847-9. Epub 2011 Feb 23.

Theanine is a candidate amino acid for pharmacological stabilization of mast cells.

Kim NH1, Jeong HJ, Kim HM.

Author information

1

Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.

Abstract

The increasing occurrences of allergic disorders may be attributed to exposure to environmental factors that contribute to the pathogenesis of allergy. The health benefits of green tea have been widely reported but are largely unsubstantiated. Theanine is the major amino acid present in green tea. In this study, we investigated the role of theanine in both IgE- and non- IgE-induced allergic response. Theanine inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling responses. IgE-mediated passive cutaneous anaphylaxis was inhibited by the oral administration or pharmaceutical acupuncture of theanine. Histamine release from mast cells was decreased with the treatment of theanine. Theanine also repressed phorbol 12-myristate 13-acetate and calcium ionophore A23187-induced TNF-α, IL-1β, IL-6, and IL-8 secretion by suppressing NF-κB activation. Furthermore, theanine suppressed the activation of caspase-1 and the expression‎ of receptor interacting protein-2. The current study demonstrates for the first time that theanine might possess mast cell-stabilizing capabilities.

참고) 

AMPA receptor

- 중추신경계에서 빠른 시냅스 전달에 관여하는 글루타메이트(glutamate)의 이온성막관통 수용체(ionotropic transmembrane receptor)이며 뇌의 많은 부분에서 발견됨. 주로 간질발작과 관련되어 있으며 최근에는 만성통증과 연관되어 있다고 연구됨. 

Amino Acids. 2009 Jan;36(1):21-7. doi: 10.1007/s00726-007-0020-7. Epub 2008 Jan 15.

Theanine, gamma-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats.

Yamada T1, Terashima T, Kawano S, Furuno R, Okubo T, Juneja LR, Yokogoshi H.

Author information

1

Laboratory of Nutritional Biochemistry, Ministry of Education, Culture, Sports, Science and Technology of Japan, University of Shizuoka, Shizuoka, Japan.

Abstract

Theanine (gamma-glutamylethylamide) is one of the major amino acid components in green tea and can pass through the blood-brain barrier. Recent studies suggest that theanine affects the mammalian central nervous system; however, the detailed mechanism remains unclear. In this study, we demonstrated the effect of theanine on neurotransmission in the brain striatum by in vivo brain microdialysis. Theanine injection into the rat brain striatum did not increase the concentration of excitatory neurotransmitters in the perfusate. On the other hand, theanine injection increased the concentration of glycine in the perfusate. Because it has been reported that theanine promotes dopamine release in the rat striatum, we investigated the glycine and dopamine concentrations in the perfusate. Co-injection of glycine receptor antagonist, strychnine, reduced theanine-induced changes in dopamine. Moreover, AMPA receptor antagonist, which regulates glycine and GABA release from glia cells, inhibited these effects of theanine and this result was in agreement with the known inhibitory effect of theanine at AMPA receptors.

NMDA 수용체

- 신경세포에서 발견되는 글리신과 글루타메이트가 결합하면 활성화되는 글루타메이트(glutamate)수용체 및 이온채널 단백질임. 신경의 가소성을 조절하고 기억작용에 중요한 역할. 

- 이 수용체에 마그네슘이 차단되고 칼슘이 유입되면 활성화되어 알츠하이머, 파킨슨, 헌팅턴 병과 같은 신경 퇴행성 질환을 유발함. 또한 우울증, 만성통증과도 연관되어 있음. 

Molecules. 2018 Mar; 23(3): 512. 

Published online 2018 Feb 25. doi: 10.3390/molecules23030512

PMCID: PMC6017384

PMID: 29495349

Neuroprotective Effects and Mechanisms of Tea Bioactive Components in Neurodegenerative Diseases

Shu-Qing Chen, Ze-Shi Wang, Yi-Xiao Ma, Wei Zhang, Jian-Liang Lu, Yue-Rong Liang,* and  Xin-Qiang Zheng*

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Abstract

As the population ages, neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) impose a heavy burden on society and families. The pathogeneses of PD and AD are complex. There are no radical cures for the diseases, and existing therapeutic agents for PD and AD have diverse side effects. Tea contains many bioactive components such as polyphenols, theanine, caffeine, and theaflavins. Some investigations of epidemiology have demonstrated that drinking tea can decrease the risk of PD and AD. Tea polyphenols can lower the morbidity of PD and AD by reducing oxidative stress and regulating signaling pathways and metal chelation. Theanine can inhibit the glutamate receptors and regulate the extracellular concentration of glutamine, presenting neuroprotective effects. Additionally, the neuroprotective mechanisms of caffeine and theaflavins may contribute to the ability to antagonize the adenosine receptor A2AR and the antioxidant properties, respectively. Thus, tea bioactive components might be useful for neuronal degeneration treatment in the future. In the present paper, the neuro protection and the mechanisms of tea and its bioactive components are reviewed. Moreover, the potential challenges and future work are also discussed.

Kainate 수용체(카이닌산 수용체)

- 비 NMDA수용체로 신경전달물질 글루타메이트에 반응하는 이온성 수용체임. 신경전달 억제물질인 GABA의 방출을 조절하여 신경전달을 억제하는 작용과 관련되어 있음. AMPA수용체와는 다르게 신호전달에 중요한 역할을 하지 않음. 

4) 케르세틴

- 케르세틴은 과일의 색소인 플라보노이드로 양파, 사과, 녹차, 케일, 견과류, 은행에 많이 함유.

- 강력한 항산화제이며 자연 항히스타민제로 비만세포의 막을 안정화하여 히스타민의 생성과 분비를 억제하여 항염, 항알레르기 작용을 함. 

- 위장에서 히스타민 분비를 자극하는 헬리코박터균의 성장을 억제함.

- 항암제 독성으로부터 신장세포를 보호함. 

- 그외에도 고지혈증, 고혈압, 간질성 방광염, 류마티스 관절염, 전립선염과 같이 항생제로 치료되지 않는 염증치료에 효과적임. 

케르세틴의 약물상호작용

- 항응고제(아스피린, 와파린) 작용을 강화함. 

- 스테로이드 작용시간을 연장함

- 항암제 작용을 강화함. 

- 퀴놀론의 효과를 감소시키며 간으로 대사되는 약물과 함께 사용하면 간에 부담을 줌. 

참고) 퀴놀론 항생제

- 요로감염 등에 주로 사용하는 항생제로 레보플록사신(레바킨), 시프로프록사신(시프로), 목시플로사신(아벨록스), 디플라플로사신(박스델라), 제미플록사신(팩티브), 오플록사신 등이 있으며 우리나라에는 복제약이 60여가지 있음. 

- 장기복용시 심한 저혈당, 주의력결핍, 기억장애, 신경과민, 불안, 초조, 방향감각 장애 등을 유발함. 

5) 루테올린

- 비만세포의 막을 안정시켜 히스타민 분비를 억제하는 작용을 해 히스타민 증후군 치료에 사용되는 성분. 루테올린은 식물성 영양물질인 플라보노이드 계통의 노란색의 불투명한 물질로 '타임, 로즈메리, 세이지'같은 허브에 다량 들어있고 고추, 파슬리, 샐러리 등과 같은 녹황색 채소에도 들어있음. 

- 인체내에서 항산화작용, 활성산소제거, 탄수화물의 신진대사 조절, 면역체계를 조절하는 기능

- 암세포의 성장을 억제

- 다발성 경화증에도 효과적

- 루테올린은 뇌와 관련된 히스타민 증후군 치료에 응용할 수 있음. 

Cent Eur J Immunol. 2017; 42(1): 24–29. 

Published online 2017 May 8. doi: 10.5114/ceji.2017.67315

PMCID: PMC5470611

PMID: 28680328

Anti-allergic effect of luteolin in mice with allergic asthma and rhinitis

Tae Young Jang, Ah-Yeoun Jung, Tae-Suk Kyung, Dae-Young Kim, Jun-Ha Hwang, and  Young Hyo Kim

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Abstract

Aim of the study

We aimed to eval‎uate the anti-allergic effect of luteolin treatment in mice with allergic asthma and rhinitis.

Material and methods

Thirty-two BALB/c mice (n = 8 for each group) were used. Mice in group A (nonallergic group) were exposed to saline, while those in Group B (allergic group) were exposed to ovalbumin (OVA) intraperitoneal (i.p.) injection and intranasal (i.n.) challenge. Null treatment group (Group C) received sterile saline (150 μl) i.p. injection, 30 minutes before each i.n. challenge. Finally, the treatment group (Group D) received luteolin (0.1 mg/kg) by i.p. injection, 30 minutes before each i.n. challenge. We eval‎uated the number of inflammatory cells including eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage (BAL) fluid, the titers of IL-4, IL-5 and IL-13 in lung homogenate, and we also eval‎uated histopathologic findings, including infiltration of inflammatory cells into the pulmonary parenchyma and nasal mucosa.

Results

After the OVA challenge, the number of eosinophils, neutrophils and lymphocytes in BAL fluid was significantly increased in group B, compared to group A (p < 0.001). Mice in group C had no significant difference (p > 0.05). On the other hand, group D showed a significant decrease in all inflammatory cells compared to group B (p < 0.05). Also, group D showed a significant decrease in IL-4, IL-5 and IL-13 in their lung homogenate compared to groups B and C (p < 0.05). Group D also showed a significant decrease in inflammatory cell infiltration after luteolin treatment (p < 0.05).

Conclusion

Luteolin had an anti-allergic effect in a murine model of allergic asthma and rhinitis.

Keywords: asthma, allergic rhinitis, luteolin

6) 아연, 망간

- 히스타민 증후군 환자에게 아연과 망간을 복용하게 하는 이유는 '구리'의 작용을 약화시키기 위함. 

- 아연과 망간의 흡수과정에서 구리와 경쟁함. 

- 히스타민 농도가 높은 환자는 '구리'농도가 높음

- 구리는 히스타민을 만드는 중요한 미네랄임. 

7) 비타민 C

- 비타민 C는 혈중 히스타민 농도를 낮추는 효과

- 2g의 비타민 C를 복용하면 혈중 히스타민 농도를 40% 낮출 수 있고 이 효과는 4시간 유지됨.

J Int Med Res. 2018 Sep; 46(9): 3640–3655. 

Published online 2018 Jun 27. doi: 10.1177/0300060518777044

PMCID: PMC6136002

PMID: 29950123

Intravenous vitamin C in the treatment of allergies: an interim subgroup analysis of a long-term observational study

Claudia Vollbracht,1 Martin Raithel,2 Bianka Krick,1 Karin Kraft,3 and  Alexander F. Hagel4

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Short abstract

Objective

Oxidative stress appears to be a key factor in the pathogenesis of allergic diseases and a potential therapeutic target in allergy treatment. Allergic diseases are reportedly associated with reduced plasma levels of ascorbate, which is a key physiological antioxidant. Ascorbate prevents excessive inflammation without reducing the defensive capacity of the immune system.

Methods

An interim analysis of a multicenter, prospective, observational study was conducted to investigate the change in disease-specific and nonspecific symptoms (fatigue, sleep disorders, depression, and lack of mental concentration) during adjuvant treatment with intravenous vitamin C (Pascorbin®; Pascoe, Giessen, Germany) in 71 patients with allergy-related respiratory or cutaneous indications.

Results

Between the start and end of treatment, the mean sum score of three disease-specific symptoms decreased significantly by 4.71 points and that of four nonspecific symptoms decreased significantly by 4.84 points. More than 50% of patients took no other allergy-related medication besides vitamin C.

Conclusions

Our observations suggest that treatment with intravenous high-dose vitamin C reduces allergy-related symptoms. Our observations form a basis for planning a randomized controlled clinical trial to obtain more definitive evidence of the clinical relevance of our findings. We also obtained evidence of ascorbate deficiency in allergy-related diseases.

Trial registration: Clinical Trials NCT02422901.

Keywords: Ascorbic acid, allergic rhinitis, allergic asthma, dermatitis, eczema, human, pruritus, intravenous administration

S-adenosylmethionine(SAMe)

- s-아데노실메티오닌은 아데노신과 메티오닌이 결합한 아미노산.

- 모든 조직의 체액에 포함되어 있지만 특히 특히 간과 뇌에 많이 존재하며 핵산과 인지질, 호르몬 등의 합성에 이용됨. 

- SAMe에는 뇌와 관절, 간건강을 유지하는 효능이 있어 유럽에서는 우울증, 관절염, 간기능 개선 등의 의약품으로 사용됨. 미국에서는 건강보조제

- 히스타민 증후군에서 SAMe는 히스타민이 대사되는 NMHT(N-methylhistamine trasnferase)효소의 작용에 관여함. 이 효소는 SAMe으로부터 메틸기를 받아 인체에서 히스타민의 활동성을 억제함. 그러므로 이 효소에 문제가 있을때 나타나는 우울증, 만성통증을 동반한 히스타민 증후군이 나타날 수 있음. 부작용은 약간의 위장장애외에 거의 없음.

메이요 클리닉

Overview

S-adenosyl-L-methionine (SAMe) is a compound found naturally in the body. SAMe helps produce and regulate hormones and maintain cell membranes.

A synthetic version of SAMe is available as a dietary supplement in the U.S. In Europe, SAMe is a prescription drug.

SAMe can be taken orally, intravenously or through a muscular injection. People generally use SAMe to treat osteoarthritis, liver disease and depression. However, SAMe can also interact with antidepressant medications.

Evidence

Research on SAMe use for specific conditions shows:

• Depression. While research has shown that SAMe has a positive effect in treating depression, most studies weren't well-designed and included a small number of people.
• Liver disease. It's not clear if SAMe is beneficial for people who have liver disease.
• Osteoarthritis. Many studies comparing the use of SAMe with nonsteroidal anti-inflammatory drugs showed that each provided similar pain relief and improvement in joint function, but SAMe produced fewer side effects. A smaller number of studies haven't shown the same results.

Generally safe

SAMe appears to be safe and might be effective in treating osteoarthritis and depression. However, SAMe might interact with use of antidepressants. Don't use SAMe and prescription antidepressants together.

Safety and side effects

Side effects from SAMe are rare and, if they occur, usually mild.

SAMe can cause:

• Upset stomach
• Nausea
• Mild insomnia
• Dizziness
• Irritability
• Anxiety
• Sweating
• Constipation
• Diarrhea