호메시스 - 우리를 둘러싼 이슈들(GMP식품, 비타민, 미네랄, 보충제, 콜레스테롤, 소금 등)

[문형철]

BEYOND REASON

유전자조작식품을 어떻게 볼것인가? 

현대인이 일단 유전자조작식품을 피하는 것은 거의 불가능한 상황임. 

Genetically modified organisms --> genetically manipulated organisms

우리가 할 수 있는 것은 호메시스를 일상적으로 작동시켜서 우리 몸에 GMO 때문에 라운드업때문에 그리고 POPs때문에 세포수준에서 문제가 발생했을때 초기에 우리 세포가 즉각 이런 상황을 감지하여 바로잡도록 도와주는 것 그 외에는 방법이 없음. 

2012년 9월 프랑스 캉대학교 세랄리니 교수 연구팀이 발표한 GMO 옥수수 논문이 세계를 발칵 뒤집어 놓음

1-s2.0-S0278691512005637-main.pdf

The health effects of a Roundup-tolerant genetically modified maize (from 11% in the diet), cultivated

with or without Roundup, and Roundup alone (from 0.1 ppb in water), were studied 2 years in rats. In females, all treated groups died 2–3 times more than controls, and more rapidly. This difference was visible in 3 male groups fed GMOs. All results were hormone and sex dependent, and the pathological profiles were comparable. Females developed large mammary tumors almost always more often than and before controls, the pituitary was the second most disabled organ; the sex hormonal balance was modified by GMO and Roundup treatments. In treated males, liver congestions and necrosis were 2.5–5.5 times higher. This pathology was confirmed by optic and transmission electron microscopy. Marked

and severe kidney nephropathies were also generally 1.3–2.3 greater. Males presented 4 times more large palpable tumors than controls which occurred up to 600 days earlier. Biochemistry data confirmed very significant kidney chronic deficiencies; for all treatments and both sexes, 76% of the altered parameters were kidney related. These results can be explained by the non linear endocrine-disrupting effects of Roundup, but also by the overexpression‎ of the transgene in the GMO and its metabolic consequences.

몬산토 회사, GMO옥수수, 라운드업 제초제

비타민 보충제

예를들어 토마토를 많이 먹는 사람이 암에 걸릴 위험이 낮아진다는 연구를 발표하면 과학자들은 토마토의 어떤 성분이 어떤 기전으로 암의 위험성을 낮추는지 증거가 있어야 과학적인 주장이라고 받아들여짐.그래서 토마토의 특정물질 리코펜의 화학적 구조를 밝히고 쥐에게 투여했을때 세포내 신호전달체계가 어떻게 달라지고 유전자 발현이 어떻게 달라져 암의 위험성이 줄어든다고 연구하여 발표해야 비로소 과학의 세계로 입성함. 그러면 기업들은 리코펜 보충제나 신약이라는 이름으로 출시함. 연구자들도 이런 연구를 매우 좋아함. 

그런데 리코펜 성분을 먹는 사람과 토마토를 먹는 사람 어떤 것이 더 효과적일까? 

베타카로틴 사례

코펜하겐 쇼크

Review 

February 28, 2007

Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention

Systematic Review and Meta-analysis

Goran Bjelakovic, MD, DrMedSci; Dimitrinka Nikolova, MA; Lise Lotte Gluud, MD, DrMedSci; et alRosa G. Simonetti, MD; Christian Gluud, MD, DrMedSci

Author Affiliations

JAMA. 2007;297(8):842-857. doi:10.1001/jama.297.8.842

 

Full Text

Abstract

Context Antioxidant supplements are used for prevention of several diseases.

Objective To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials.

Data Sources and Trial Selection We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials.

Data Extraction We included 68 randomized trials with 232 606 participants (385 publications).

Data Synthesis When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.

Conclusions Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.

기전이 어떻게 되든지 간에 어떤 식품이 건강에 좋다고 해서 그 식품에 많이 들어있다고 알려진 어떤 특정성분만을 추출해서 보충제로 먹으면 더 좋을 것이라는 환상은 버려야 함. 

철분이야기

활성산소는 반응성이 높은 철분을 만나면 아주 파괴적인 물질들을 만들어내면서 우리 세포를 구성하는 유전자, 단백질, 지질들을 공격함. 그래서 비타민 C를 비롯한 항산화 물질도 철분이 많이 존재하면 산화 스트레스를 높이는 파괴적인 물질을 만들어내는데 기여함. 

일반적으로 철분은 인체내에서 단백질에 단단하게 결합된 상태로 존재하고 반응성이 높은 철분이 존재한다고 해도 그 존재시간이 찰나의 순간이라고 생각함. 즉 철분과 결합하는 단백질이 100% 포화된 다음에야 반응성이 높은 철분의 형태로 존재할 수 있지 그렇지 않으면 문제가 없다는 것. 인체에서 철분이 가지는 위치는 어떤 미량원소보다 더 중요함. 바로 생존에 필수적인 산소를 운반하는데 관여하기 때문임. 사람들은 철분이 많으면 많을수록 좋다는 인식을 함. 임신을 하면 누구나 철분보충제를 먹고 밀가루, 시리얼에는 철분을 첨가해서 먹는 시대임. 

정말 철분을 많이 먹으면 좋은 것일까? 

음식속의 철분 흡수율은 우리 인체의 철분 필요량에 따라 민감하게 반응함. 우리 몸이 철분이 필요하다고 인식하면 흡수율이 증가되고 그렇지 않으면 철분 흡수율이 떨어짐. 특히 식물성 식품에 들어있는 철분의 흡수율은 평상시에는 흡수율이 10%미만이지만 임신시와 같이 철분이 많이 필요하면 흡수율이 증가함. 동물성 식품의 철분은 기본 흡수율이 높아서 동물성 식품을 많이 먹으면 인체내의 철분 축적량은 증가함. 요즘에는 거의 대부분의 가공식품에 상당량의 철분을 인위적으로 첨가함. 

Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Sorrel ML Namaste,  Fabian Rohner,  Jin Huang,  Nivedita L Bhushan, Rafael Flores-Ayala,  Roland Kupka,  Zuguo Mei,  Rahul Rawat,  Anne M Williams, Daniel J Raiten ... Show more

Author Notes

The American Journal of Clinical Nutrition, Volume 106, Issue suppl_1, July 2017, Pages 359S–371S, https://doi.org/10.3945/ajcn.116.141762

Published:

 

14 June 2017

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ABSTRACT

Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation.

Objective: We assessed the relation between ferritin concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and investigated adjustment algorithms to account for these effects.

Design: Cross-sectional data from 15 surveys for PSC (n = 27,865) and 8 surveys for WRA (24,844), from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to estimate depleted iron stores (ferritin concentration <12 μg/L in PSC and <15 μg/L in WRA) in inflammation and malaria settings as follows: 1) increase ferritin-concentration cutoff to <30 μg/L; 2) exclude individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L; 3) apply arithmetic correction factors; and 4) use a regression correction approach.

Results: Depleted iron-store estimates incrementally increased as CRP and AGP deciles decreased (4% compared with 30%, and 6% compared with 29% from highest compared with lowest CRP deciles for pooled PSC and WRA, respectively, with similar results for AGP). Depending on the approach used to adjust for inflammation (CRP plus AGP), the estimated preval‎ence of depleted iron stores increased by 7–25 and 2–8 absolute median percentage points for PSC and WRA, respectively, compared with unadjusted values. Adjustment for malaria in addition to CRP and AGP did not substantially change the estimated preval‎ence of depleted iron stores.

Conclusions: Our results lend support for the use of internal regression correction to estimate the preval‎ence of depleted iron stores in regions with inflammation. This approach appears to mathematically reflect the linear relation of ferritin concentrations with acute-phase proteins. More research is warranted to validate the proposed approaches, but this study contributes to the evidence base to guide decisions about how and when to adjust ferritin for inflammation.

페리틴 지수

체내에 축적된 철분량이 얼마나 되는가를 측정하는 지표검사임. 그런데 이 페리틴은 인체에서 염증반응이 일어났을때 증가하는 물질임. 왜 염증반응시 페리틴이 증가할까? 염증반응시 페리틴이 높아지는 상황이라는 것이 바로 인체내에서 반응성이 높은 철분이 발생하는 상황임. 당뇨병은 혈중 페리틴이 증가해있는 대표적인 만성질환임. 당뇨병환자들은 체내에 반응성이 높은 철분이 많고 이 환자들이 비타민 C를 보충제로 장기간 먹으면 비타민 C가 오히려 나쁜 쪽(산화스트레스를 높이는 방향)으로 작용할 가능성이 있음. 

당뇨병이 있는 사람들이 비타민 C를 10년이상 보충제로 먹은 경우 당뇨병 합병증인 심장병, 뇌졸중으로사망할 위험성이 2~3배 높아짐. 이전 연구결과들은 당뇨병환자들이 비타민 C를 복용하면 산화스트레스나 염증이 감소된다고 보고하고 있음. 

근육검사 

당뇨환자가  비타민 C를 10년이상 보충제로 복용할 경우 심장병, 뇌졸중의 위험성이 높아진다  YES

Vitamin C Intake, Circulating Vitamin C and Risk of Stroke: A Meta‐Analysis of Prospective Studies

Guo‐Chong Chen, MPH, Da‐Bing Lu, MD, PhD, [...], and Qing‐Fang Liu, MM

Additional article information

Abstract

Background

Though vitamin C supplementation has shown no observed effects on stroke prevention in several clinical trials, uncertainty remains as to whether long‐term, low‐dose intake influences the development of stroke among general populations. Furthermore, the association between circulating vitamin C and the risk of stroke is also unclear. For further clarification of these issues, we conducted a meta‐analysis of prospective studies.

Methods and Results

PubMed and EMBASE databases were searched, and the bibliographies of the retrieved articles were also reviewed to identify eligible studies. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were computed with a random‐effects model. The summary RR for the high‐versus‐low categories was 0.81 (95% CI: 0.74 to 0.90) for dietary vitamin C intake (11 studies), and 0.62 (95% CI: 0.49 to 0.79) for circulating vitamin C (6 studies). The summary RR for each 100 mg/day increment in dietary vitamin C was 0.83 (95% CI: 0.75 to 0.93) (10 studies), and for each 20 μmol/L increment in circulating vitamin C was 0.81 (95% CI: 0.75 to 0.88) (5 studies). Few studies reported results for vitamin C supplements (RR for high‐versus‐low intake=0.83, 95% CI: 0.62 to 1.10, 3 studies).

Conclusions

This meta‐analysis suggests significant inverse relationships between dietary vitamin C intake, circulating vitamin C, and risk of stroke.

Keywords: antioxidants, diet, meta‐analysis, prevention, stroke

근육검사

당뇨병환자가 비타민 C를 많이 복용하면 활성산소가 많아져 건강에 해롭다 YES

당뇨병 환자가 비타민 C를 많이 복용하면 활성산소를 제거해주기 때문에 건강에 이롭다 NO

당뇨병 환자에게 흔하게 볼 수있는 합병증 중 철결핍성 빈혈이 있음. 이 빈혈은 철분이 부족해서가 아니라 철분을 사용하지 못해서 발생하는 빈혈임. 우리가 던져야 할 질문은 왜 염증반응이 존재할때 인체내에서는 이런 현상이 일어나는가?라는 것임. 만성염증이 존재할때 철 결핍성 빈혈까지 초래될 정도로 우리 몸이 철분을 이용하는 상황을 꺼리는 방향으로 반응을 한다는 것은 이때 철분을 평소처럼 이용하는 것은 상당한 위험부담이 존재한다는 것을 우리몸이 알고 있다는 증거임. 인체에서 철분이 위험해지는 대표적인 상황이 바로 반응성이 높은 철분이 생성되는 상황인데 당뇨병 환자는 반응성이 높은 철분이 증가해 있는 것임. 

철분이 부족해서 생기는 철 결핍성 빈혈은 전세계적으로 가장 흔한 질병중 하나임. 하지만 철 결핍성 빈혈과 같이 미량원소가 부족해서 발생하는 질병은 병중에서 가장 치료가 용이한 종류임. 그 특정 성분만 일정기간 공급해주면 말끔히 좋아짐. 

그런데 20세기 후반 연구에 의하면 철분은 부족한 것도 문제지만 너무 많은 것도 문제가 됨. 

Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells 

Douglas B. Kell*a  and  Etheresia Pretorius*b  

 Author affiliations

Abstract

"Serum ferritin" presents a paradox, as the iron storage protein ferritin is not synthesised in serum yet is to be found there. Serum ferritin is also a well known inflammatory marker, but it is unclear whether serum ferritin reflects or causes inflammation, or whether it is involved in an inflammatory cycle. We argue here that serum ferritin arises from damaged cells, and is thus a marker of cellular damage. The protein in serum ferritin is considered benign, but it has lost (i.e. dumped) most of its normal complement of iron which when unliganded is highly toxic. The facts that serum ferritin levels can correlate with both disease and with body iron stores are thus expected on simple chemical kinetic grounds. Serum ferritin levels also correlate with other phenotypic readouts such as erythrocyte morphology. Overall, this systems approach serves to explain a number of apparent paradoxes of serum ferritin, including (i) why it correlates with biomarkers of cell damage, (ii) why it correlates with biomarkers of hydroxyl radical formation (and oxidative stress) and (iii) therefore why it correlates with the presence and/or severity of numerous diseases. This leads to suggestions for how one might exploit the corollaries of the recognition that serum ferritin levels mainly represent a consequence of cell stress and damage.

밀의 배아부분과 배젖부분 이야기

밀의 배아부분은 다양한 미량원소의 보고임. 그런데 배아부분을 그대로 두면 밀가루가 변질될 우려가 높아 19세기 후반부터 도정과정에서 제거해버림. 바로 하얀 밀가루임. 그 결과 밀가루의 영양소는 제분과정에서 사라져 문제를 일으킴. 배아부분을 제거하지 않은 밀가루는 검정회색임. 

엽산 이야기

엽산은 비타민 B로 녹색 잎을 가진 채소에 많다고 해서 엽산이라고 부름. 엽산은 채소외에 콩, 과일, 동물의 간에도 많음. 엽산은 유전정보를 담고 있는  DNA 합성에 필수적인 성분임. 그래서 세포가 왕성하게 분열하는 시기에 엽산이 부족하지 않게 공급하는 것은 중요함. 

1996년 More folic acid for everyone, now라는 논문

1998년 시리얼, 밀가루에 엽산을 의무적으로 첨가하는 정책을 폄. 미국 질병관리본부는 그 결과 신경관결손을 가지고 태어나는 아이가 급격하게 줄었다고 자랑했었음.

J Nutr. 1996 Mar;126(3):751S-755S. doi: 10.1093/jn/126.suppl_3.751S.

More folic acid for everyone, now.

Oakley GP Jr1, Adams MJ, Dickinson CM.

Author information

Abstract

Research during the last 5 years has made it clear that people who do not take folic acid supplements are at increased risk for functional folate deficiency, which has been proven to cause spina bifida and anencephaly and also has been associated with an increased risk for occlusive cardiovascular disease. The overriding folate policy issue is how to increase dramatically the folate consumption of 75% of the population who are now consuming 0.4 mg of folic acid in a supplement. The most expeditious way to increase consumption is through fortification of a food staple. Public health programs are also needed to educate people about the vital importance of increased consumption of folic acid vitamin supplements and of food rich in natural folates. It is urgent that fortification of cereal-grain products be implemented now. The level proposes by FDA would accomplish some prevention, but much more prevention would occur if the fortification were 2.5 times that level. Fortification at the higher level would prevent about 1000 spina bifida and anencephaly birth defects each year and perhaps as many as 50,000 premature deaths each year from coronary disease. Available data have not demonstrated that increasing consumption of folic acid by 0.1 to 0.25 mg of folic acid a day is harmful. If a policy needs to be established on the assumption that people who take vitamin supplements could be harmed, a good policy option ia available; require that all folic acid vitamin supplements also contain 0.4 mg of vitamin B-12.

 그런데 10년 후 2008년 Is folic acid good for everyone?라는 논문이 발표됨. 

High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer.

In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children.

Is folic acid good for everyone? 

A David Smith,  Young-In Kim,  Helga Refsum

The American Journal of Clinical Nutrition, Volume 87, Issue 3, March 2008, Pages 517–533, https://doi.org/10.1093/ajcn/87.3.517

Published:

 

01 March 2008

 Article history

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ABSTRACT

Fortification of food with folic acid to reduce the number of neural tube defects was introduced 10 y ago in North America. Many countries are considering whether to adopt this policy. When fortification is introduced, several hundred thousand people are exposed to an increased intake of folic acid for each neural tube defect pregnancy that is prevented. 

Are the benefits to the few outweighed by possible harm to some of the many exposed? In animals, a folic acid–rich diet can influence DNA and histone methylation, which leads to phenotypic changes in subsequent generations. In humans, increased folic acid intake leads to elevated blood concentrations of naturally occurring folates and of unmetabolized folic acid. High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer. 

In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children. Folate has a dual effect on cancer, protecting against cancer initiation but facilitating progression and growth of preneoplastic cells and subclinical cancers, which are common in the population. Thus, a high folic acid intake may be harmful for some people. Nations considering fortification should be cautious and stimulate further research to identify the effects, good and bad, caused by a high intake of folic acid from fortified food or dietary supplements. Only then can authorities develop the right strategies for the population as a whole.

암에 있어서 엽산과다는 이중효과를 보임. 암이 처음 시작되는 단계에서는 암발생을 억제하는 효과가 있으나 이미 암세포가 존재하는 상황에서는 오히려 암세포가 증식하는데 도와주는 역할을 할 가능성이 있음. 

근육검사

암이 존재하는 상황에서 엽산은 좋은 선택이다 yes

암이 처음 시작되는 단계에서 엽산은 좋은 선택이다 yes

임신때는 어떨까? 

임신시 먹는 엽산은 신경관결손을 가진 기형아 발생을 예방하는데 도움이 됨. 그리고 엽산은 유전자 발현에 매우 중요한 영향을 미침. 그러나 그 기전을 보면 엽산만이 있는 것이 아니고 여러가지 다양한 영양소들의 역할도 중요함. 이들 중 엽산만 골라서 보충제로 과다복용하면 영양소들간의 밸런스가 깨짐. 

Am J Clin Nutr. 2013 Nov;98(5):1272-81. doi: 10.3945/ajcn.113.065623. Epub 2013 Sep 4.

Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis.

Crider KS1, Cordero AM, Qi YP, Mulinare J, Dowling NF, Berry RJ.

Author information

Abstract

BACKGROUND: 

Childhood asthma has become a critical public health problem because of its high morbidity and increasing preval‎ence. The impact of nutrition and other exposures during pregnancy on long-term health and development of children has been of increasing interest.

OBJECTIVE: 

We performed a systematic review and meta-analysis of the association of folate and folic acid intake during pregnancy and risk of asthma and other allergic outcomes in children.

DESIGN: 

We performed a systematic search of 8 electronic databases for articles that examined the association between prenatal folate or folic acid exposure and risk of asthma and other allergic outcomes (eg, allergy, eczema, and atopic dermatitis) in childhood. We performed a meta-analysis by using a random-effects model to derive a summary risk estimate of studies with similar exposure timing, exposure assessment, and outcomes.

RESULTS: 

Our meta-analysis provided no evidence of an association between maternal folic acid supplement use (compared with no use) in the prepregnancy period through the first trimester and asthma in childhood (summary risk estimate: 1.01; 95% CI: 0.78, 1.30). Because of substantial heterogeneity in exposures and outcomes, it was not possible to generate summary measures for other folate indicators (eg, blood folate concentrations) and asthma or allergy-related outcomes; however, the preponderance of primary risk estimates was not elevated.

CONCLUSIONS: 

Our findings do not support an association between periconceptional folic acid supplementation and increased risk of asthma in children. However, because of the limited number and types of studies in the literature, additional research is needed.

엽산부족을 예방하기 위해서는 엽산이 많이 든 음식을 충분히 먹는 것이 가장 과학적인 결론임. 

근육검사 

임신시 엽산보충제를 먹는 것은 좋은 선택이다 yes

콜레스테롤 신화

20 세기에 들어서 심장병으로 사망하는 환자가 급증함. 심장병으로 사망한 사람들을 부검해보면 관상동맥에 지방이 잔뜩 끼어 있는 것을 볼 수 있음. 콜레스테롤 가설이 생김

20세기 초 러시아 과학자가 토끼에게 동물성 음식을 먹이고 혈관에 동맥경화가 생기고 식물성 지방을 먹였을때는 동맥경화가 발생하지 않는다고 발표함. 토끼에게 고기를 먹이고 동맥경화가 생겼다고 발표한 황당한 주장을 한 것임. 하지만 세상은 이미 동물성 지방과 콜레스테롤에 주목해버렸음. 

1953년 안셀키즈(Ancel Keys)는 Atherosclerosis, a Problem in newer public health라는 논문을 발표함. 이 논문은 의도적으로 6개국을 조작한 것으로 밝혀졌지만 동물성 지방-혈중콜레스테롤-심장병으로 이어지는 패러다임의 완성에 결정적인 역할을 함. 그리고 현대인들은 지방섭취를 줄이고 대신 탄수화물, 단순당(빵, 음료수, 과자)의 섭취량이 급증함. 

1960년대 원시부족들의 식생활을 보면 동물성 식품을 칼로리원으로 살아가는 부족들이 많음. 그들은 혈중 콜레스테롤 수치가 낮고 심장병 위험더 매우 드믐. 그런데 이 원시부족들이 도시로 이주해 현대인의 식생활을 하면 콜레스테롤 수치가 올라가고 심장병도 많이 나타남. 

1990년 인공적으로 수화시킨 식물성 기름으로 인한 트랜스지방이 동물성 식품안에 포함된 포화지방보다 더 위험하다는 연구결과가 발표되면서 혼란에 빠짐. 그리고 탄수화물 섭취량의 증가는 1980년대부터급속히 증가하기 시작한 미국내 비만의 가장 중요한 원인으로 지목되기 시작함. 

2015년 미국보건부 산하 '다이어트 가이드라인 자문위원회'라는 곳에서 콜레스테롤 함유량이 높은 음식에 대한 경고를 철회한다고 발표함. 콜레스테롤이 많이 함유된 음식은 동물성 식품, 계란, 새우, 가재 등'임. 참고로 콜레스테롤과 포화지방은 전혀 다른 것임. 다이어트 가이드라인 자문회의 최종결론은 '콜레스테롤이 높은 음식을 제한하지 안되 여전히 포화지방이 많은 고기, 유제품 등은 제한해야 한다고 발표함.

실제로 콜레스테롤은 우리 몸에서 직접 합성하는 양이 훨씬 많음. 80%. 그리고 콜레스테롤을 먹어서는 콜레스테롤 수치가 높아지지 않음. 

그럼 포화지방이 많은 식품을 먹으면 정말 포화지방때문에 해로운 걸까? 

원시부족(에스키모, 이누이트족, 마사이족)은 포화지방 섭취율이 매우 높지만 심장병 발생율은 매우 낮은 이유를 설명할 방법이 없음. 포화지방이 원인이라기 보다는 POPs같은 지용성 화학물질이 문제일 것으로 추정함. 

Half truth is often a great lie

비타민 D 이야기

비타민 D는 현재 뜨거운 연구테마중 하나임. 메르스, 사스, 우한폐렴과 같은 신종감염성 질환을 대비하는데 비타민 D만큼 중요한 것은 없을 것임. 

세포에서 비타민 D를 가지고 일을 제대로 하려면 비타민 D수용체가 필요함. 이 비타민 D 수용체는 뼈와관계된 세포뿐 아니라 우리 몸 거의 모든 세포에 존재함. 즉 그만큼 다양한 역할을 한다는 의미임. 비타민 D는 실제로 스테로이드 호르몬임. 콜레스테롤을 전구물질로 이용하여 합성되기 때문임. 

The calcitriol receptor, more commonly known as the vitamin D receptor (VDR) and also known as NR1I1 (nuclear receptor subfamily 1, group I, member 1), is a member of the nuclear receptor family of transcription factors.^[5]  Calcitriol, the active form of vitamin D, binds to the VDR, which then forms a heterodimer with the retinoid-X receptor. This then binds to hormone response elements on DNA resulting in expression‎ or transrepression of specific gene products. The VDR not only regulates transcriptional responses but also involved in microRNA-directed post transcriptional mechanisms.^[6] In humans, the vitamin D receptor is encoded by the VDR gene.^[7]

Glucocorticoids are known to decrease expression‎ of VDR, which is expressed in most tissues of the body and regulate intestinal transport of calcium, iron and other minerals.^[8]

kato2000.pdf

The Function of Vitamin D Receptor in Vitamin D Action

Shigeaki Kato

The Journal of Biochemistry, Volume 127, Issue 5, May 2000, Pages 717–722, https://doi.org/10.1093/oxfordjournals.jbchem.a022662

Published:

 

01 May 2000

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Abstract

Vitamin D has roles in a variety of biological actions such as calcium homeostasis, cell proliferation and cell differentiation to many target tissues. Most of these biological actions of vitamin D are now considered to be exerted through the nuclear vitamin D receptor (VDR)-mediated control of target genes. VDR belongs to the nuclear hormone receptor superfamily and acts as a ligand-inducible transcription factor. For the ligand-induced transactivation of VDR, coactivator complexes have recently been shown to be essential. The function of VDR as a ligand-induced transcription factor is overviewed, and the phenotype of VDR gene knock-out mice and the VDR-mediated transcriptional and negative regulation of the key enzyme in vitamin D biosynthesis are also described, based mainly on our recent findings, to gain a better understanding of the function of VDR in the transcriptional control of vitamin D target genes.

REVIEW ARTICLE

Front. Immunol., 18 June 2013 | https://doi.org/10.3389/fimmu.2013.00148

The vitamin D receptor and T cell function

Martin Kongsbak, Trine B. Levring, Carsten Geisler and Marina Rode von Essen*

• Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

The vitamin D receptor (VDR) is a nuclear, ligand-dependent transcription factor that in complex with hormonally active vitamin D, 1,25(OH)2D3, regulates the expression‎ of more than 900 genes involved in a wide array of physiological functions. The impact of 1,25(OH)2D3-VDR signaling on immune function has been the focus of many recent studies as a link between 1,25(OH)2D3 and susceptibility to various infections and to development of a variety of inflammatory diseases has been suggested. It is also becoming increasingly clear that microbes slow down immune reactivity by dysregulating the VDR ultimately to increase their chance of survival. 

Immune modulatory therapies that enhance VDR expression‎ and activity are therefore considered in the clinic today to a greater extent. As T cells are of great importance for both protective immunity and development of inflammatory diseases a variety of studies have been engaged investigating the impact of VDR expression‎ in T cells and found that VDR expression‎ and activity plays an important role in both T cell development, differentiation and effector function. In this review we will analyze current knowledge of VDR regulation and function in T cells and discuss its importance for immune activity.

콜레스테롤이 우리 세포가 사용할 수 있는 형태의 비타민 D로 바뀌기 위해서는 몇가지 필수적인 단계를 거쳐야 함. 첫번째가 바로 햇빛(자외선)임.  그 다음 우리 몸의 간과 신장에서 일어나는 연속적인 반응을거쳐 최종적으로 우리 세포가 사용할 수 있는 형태의 비타민 D가 만들어짐. 자외선없이 어류, 달걀, 마른 표고버섯과 같은 식품을 통해 비타민 D를 제공받을 수 있음. 

놀랍게도 햇빛이 쨍쨍하기로 유명한 적도 근처에 사는 노인들의 절반이상이 비타민 D부족임. 

실내생활을 많이해서 일까요?

자외선을 많이 바르기 때문일까요? 

비타민 D음식을 덜 먹어서일까요? 

일단 혈중 콜레스테롤이 앚은 사람들은 자외선 노출이 있어도 비타민D합성 과정을 시작할 수 없음. 현대인의 혈중콜레스테롤이 이정도로 낮은 경우는 거의 없음. 기억해야 할 것은 콜레스테롤이 낮으면 안된다는 것. 

자외선 노출과 비타민 D를 포함한 식품을 먹는 것으로 우리가 얻을 수 있는 비타민 D의 형태는 우리 세포가 당장 사용할 수 있는 비타민 D의 형태가 아님. 반드시 간에서 CYP27A1, 신장에서 CYP27B1와 같은 효소들이 제대로 작동해야 함. 하루종일 선텐을 하고 비타민이 많은 생선을 먹어도 간과 신장에 문제가 있어서 효소들이 제대로 작동하지 않으면 최종적으로 우리세포에서 사용할 수 있는 비타민 D는 부족해질 것임. 

25(OH)D2 Half-Life Is Shorter Than 25(OH)D3 Half-Life and Is Influenced by DBP Concentration and Genotype

K. S. Jones, S. Assar, [...], and I. Schoenmakers

Additional article information

Abstract

Context:

There is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D).

Objective:

The objective of the study was to compare the plasma half-lives of 25(OH)D2and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status.

Participants:

Healthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study.

Interventions:

The intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days.

Main Outcome Measures:

25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured.

Results:

25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. 

Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country.

Conclusions:

25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.

비타민 D의 반감기는 6주 정도인데 비타민 D를 분해하는 효소인 CYP24A1, CYP3A4등이 많아지면 반감기가 짧아져 우리몸은 비타민 D부족증이 될 수 있음. 

Arch Biochem Biophys. 2012 Jul 1;523(1):9-18. doi: 10.1016/j.abb.2011.11.003. Epub 2011 Nov 12.

25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D.

Jones G1, Prosser DE, Kaufmann M.

Author information

Abstract

CYP24A1 is the cytochrome P450 component of the 25-hydroxyvitamin D(3)-24-hydroxylase enzyme that catalyzes the conversion of 25-hydroxyvitamin D(3) (25-OH-D(3)) and 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) into 24-hydroxylated products, which constitute the degradation of the vitamin D molecule. This review focuses on recent data in the CYP24A1 field, including biochemical, physiological and clinical developments. Notable among these are: the first crystal structure for rat CYP24A1; mutagenesis studies which change the regioselectivity of the enzyme; and the finding that natural inactivating mutations of CYP24A1 cause the genetic disease idiopathic infantile hypercalcemia (IIH). The review also discusses the emerging correlation between rising serum phosphate/FGF-23 levels and increased CYP24A1 expression‎ in chronic kidney disease, which in turn underlies accelerated degradation of both serum 25-OH-D(3) and 1,25-(OH)(2)D(3) in this condition. This review concludes by eval‎uating the potential clinical utility of blocking this enzyme with CYP24A1 inhibitors in various disease states.

만약 비타민 D를 활성화시키는 효소를 방해하는 화학물질이 지속적으로 존재하는 상황, 비타민 D가 분해되는데 관여하는 효소의 기능을 촉진시키는 그 어떤 화학물질이 지속적으로 존재하는 상황이라면 어떤일이 발생할까요? 

바로 POPs 중에 비타민 D 분해효소의 기능을 촉진시키는 종류가 있음. 저는 현재 전세계적인 비타민 D부족의 가증 중요한 원인은 자외선 노출부족, 음식섭취 부족이 아니라 POPs가 더 중요한 역할을 할 것이라고 추정함. 여기서 다시 강조하고 싶은 것은 어떤 화학물질이 비타민 D 활성화와 분해에 관여하는 효소들과 상호작용을 한다는 것은 그 화학물질의 독성과는 아무런 관계가 없음. 예를들어 GGT의 증가는 화학물질의 독성으로 인한 것이 아니라 화학물질을 배출하는 과정에서 나타나는 현상임. 

비타민 D 부족이 화학물질의 노출때문에 생겼다면 이 역시 아주 높은 농도의 화학물질이 가지고 있는 독성때문에 생기는 현상이 아니라 화학물질을 우리몸에서 배출하기 위해 우리 몸이 정상적으로 작동하는 과정 중에서 발생한 현상이라고 보아야 함. 

지금까지는 비타민 D혈중수치를 높이는 것이 중요하다고 논문이 발표되고 있음. 

만약 비타민 D 활성화 효소 또는 분해효소와 상호작용을 하는 물질때문에 비타민  D가 낮아진다면 이러한 화학물질에 대한 노출을 피해주고 몸안에 들어와 있는 화학물질의 배출을 증가시키는 노력이 필수임. 세상에는 햇빛노출이 부족하여 비타민 D가 낮아진 사람들이 많이 있음. 예를들어 현대인 지하상가에서 하루 종일 사는 사람. 이런 사람들은 일단 햇빛쬐기를 우선 하는 것이 좋음. 그것이 불가능한 사람들이 사용하는 것이 바로 비타민 D보충제임. ...

POPs에 노출되면 비만되는 이야기

비만인구가 늘어나는 것에 대해서 많은 이유를 대지만 ... 사람들만 뚱뚱해지는 것이 아님. 동물, 애완동물, 야생동물들도 뚱뚱해지고 있음. 

2002년 Paul baillie hamilton이라는 무명연구자가 가설차원의 논문 하나를 발표함

지구상에서 화학물질 생산량의 증가추세와 비만의 증가추세가 일정기간 시간차를 두고 아주 비슷하다는 그림으로 시작함. 

J Altern Complement Med. 2002 Apr;8(2):185-92.

Chemical toxins: a hypothesis to explain the global obesity epidemic.

Baillie-Hamilton PF1.

Author information

Abstract

The number of obese people worldwide has escalated recently, revealing a complex picture of significant variations among nations and different profiles among adults and children, regions, and occupations. The commonly held causes of obesity-overeating and inactivity-do not explain the current obesity epidemic. There is evidence of a general decrease in food consumption by humans and a significant decline in their overall levels of physical activity. There is also more evidence to indicate that the body's natural weight-control mechanisms are not functioning properly in obesity. Because the obesity epidemic occurred relatively quickly, it has been suggested that environmental causes instead of genetic factors maybe largely responsible. What has, up to now, been overlooked is that the earth's environment has changed significantly during the last few decades because of the exponential production and usage of synthetic organic and inorganic chemicals. Many of these chemicals are better known for causing weight loss at high levels of exposure but much lower concentrations of these same chemicals have powerful weight-promoting actions. This property has already been widely exploited commercially to produce growth hormones that fatten livestock and pharmaceuticals that induce weight gain in grossly underweight patients. This paper presents a hypothesis that the current level of human exposure to these chemicals may have damaged many of the body's natural weight-control mechanisms. Furthermore, it is posited here that these effects, together with a wide range of additional, possibly synergistic, factors may play a significant role in the worldwide obesity epidemic.

50-60년대 독성학자들이 각종 화학물질이 어떤 농도부터 독성을 나타내는지 알기 위해 많은 연구를 했었는데 그 결과들을 자세히 살펴보면 다양한 종류의 화학물질들이 저농도에서는 체중을 증가시키는 양상을 보이더라고 논문에 밝히고 있음. 참고로 체중감소는 독성을 나타내는 하나의 신호임. 

이 논문은 발표당시 주목받지 못하고 잊혀지는 듯 함. 최근 이 무명의 연구자가 발표한 가실이 점차 진실로 드러나고 있음. 고상하게 'obesogen hypothesis'라는 이름으로

History of the Obesogen Field: Looking Back to Look Forward

Jerrold J. Heindel

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Abstract

The Obesogen field developed from two separate scientific research areas, endocrine disruptors and the Developmental Origins of Health and Disease (DOHaD). Endocrine Disrupting Chemicals (EDCs) are exogenous chemicals or mixtures of chemicals that interfere with the action of hormones. Exposure to EDCs during early development (DOHaD) has been shown to increase susceptibility to a variety of diseases including infertility, asthma, breast and prostate cancer, early puberty, susceptibility to infections, heart disease, autoimmune disease, and attention deficit hyperactivity disorder/learning disability. 

The effects of EDCs on obesity and fat cell development first gained attention around the turn of the twenty-first century. In 2002 Dr. Paula Baillie-Hamilton wrote the first review article focusing on environmental chemicals and obesity. She suggested that the obesity epidemic correlated with the increased production of chemicals after World War II. Baillie-Hamilton identified studies showing that exposures to a variety of chemicals led to weight gain. Shortly after that a commentary on an article showing that nonylphenol would increase fat cell differentiation in vitro noted the Baillie-Hamilton article and made the point that perhaps obesity was due in part to exposure to EDCs. 

In 2006 the field of DOHaD/EDCs and obesity made a giant leap forward when Dr. Bruce Blumberg published a paper showing that tributyltin could lead to weight gain in mice and coined the term obesogen for a chemical that caused weight gain and lead to obesity. In 2011, the NIEHS developed the first funding initiative focused on obesogens. In the following years there have been several workshops focused on obesogens. This paper describes these early days that lead to the obesogen hypotheses and the growth of the field for a decade, leading to its prominence today, and provides some insight into where the field is moving.

Keywords: endocrine disruptor, obesogen, metabolism disruptor, developmental origins of disease, obesity

비만의 역설

French paradox 프랑스인들은 다른 유럽사람들보다 동물성 지방을 많이 섭취함에도 불구하고 심장병 발생율은 오히려 낮은 현상. 당시 연구자들은 프랑스인들이 많이 마시는 포도주때문이라고 주장함. 

비만의 역설(obesity paradox). 일단 환자가 된 사람들을 대상으로 예후를 보면 비만한 사람들이 정상체중, 마른 체중보다 더 오래 산다는 것이 비만의 역설임. 성인이 되어서 체중이 빠지는 사람들의 사망율이 제일 높고 조금씩 증가하는 사람들의 사망율이 제일 낮다는 연구도 있음. 

지용성 화학물질의 관점에서 보면 비만조직은 일종의 버퍼역할, 방어역할을 함. POPs와 같은 화학물질(반감기는 수년에서 수십년)이 들어오면 지방조직에 머뭄. 

건강한 비만

인슐린 저항성과 관련된 당뇨, 고지혈증, 고혈압과 같은 질병은 뚱뚱한 사람일수록 많지만 모든 뚱뚱한 사람들이 그런 문제를 가진 것은 아님. 즉 만성염증, 인슐린 저항성이 없는 건강한 비만이 있을 수 있음. 또한 동일한양의 비만조직을 가지고 있더라도 이 화학물질들이 비만세포에 안전하게 보관되어 있다면 건강한 비만이 될 수 있음. 

저농도의 화학물질에 노출되면 지방전구세포(preadipocyte)가 지방세포(adipocyte)로 분화되어 비만세포의 숫자가 늘어남. 그런데 이런 상황에서도 개인이 가진 총 지방세포의 숫자는 다를 수 있음. 한사람은 크기가 작은 100개의 지방세포를 가지고 있고 다른 사람은 크기가 큰 50개의 지방세포를 가졌다면 가능함. 이러한 경우 크기가 작은 100개의 비만세포를 가진 사람이 상대적으로 건강한 비만일 가능성이 높음. 지용성 화학물질을 보다 안전하게 보관할 수 있는 장소를 많이 확보하고 있다는 의미임. 

현재 비만한 사람이 갑자기 살을 빼면? 

지방조직에 저장된 POPs가 갑자기 혈중으로 배출되어 혈중 POPs농도가 높아짐. 이 과정에서 바디버든을 초과하면 질병이 생길 수 있음. 그래서 체중을 줄이는 속도를 늦춰야 하고 간청소, 담도청소, 대장해독과 같은 POPs 해독프로그램을 병행해야 함. 

• Short Communication
• Published: 07 September 2010

Inverse associations between long-term weight change and serum concentrations of persistent organic pollutants

• J S Lim, 
• H-K Son, 
• S-K Park, 
• D R Jacobs Jr & 
• D-H Lee 

International Journal of Obesity volume 35, pages744–747(2011)Cite this article

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Abstract

There is emerging evidence that persistent organic pollutants (POPs) can increase the risk of various chronic diseases. As POPs mainly bioaccumulate in adipose tissue, weight change can affect serum concentrations of POPs. However, there are few population-based studies on effects of long-term weight change on serum concentrations of POPs. We examined associations between self-reported weight change over 1 year and 10 years and serum concentrations of seven POPs in 1099 adults aged ⩾40. Serum concentrations of most POPs were higher in those with long-term weight loss, whereas they were lower in those with long-term weight gain. Adjusted correlation coefficients of each POP with weight change for 10 years were −0.23 (P<0.01) for trans-nonachlor, −0.16 (P<0.01) for p,p′-dichlorodiphenyldichloroethylene, and −0.21 (P<0.01) for β-hexachlorocyclohexane, −0.16 (P<0.01) for PCB169, −0.20 (P<0.01) for PCB180 and −0.17 (P<0.01) for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin. Weight change for 1 year showed similar but weaker associations, compared with those of long-term weight changes. Although both beneficial health effects after weight loss and harmful health effects after weight gain are generally expected, changes in serum concentrations of POPs in relation to weight change may act on health in directions opposite to what we expect with weight change.

마사이 부족이 현미채식을 한다면?

마사이족은 육식을 한 부족임. 유전자입장에서 두가지 측면을 고려해서 생각해야 함. 첫째, 유전자 염기서열(사람과 침팬치의 유전자 염기서열은 98%가 일치함), 둘째 그 유전자의 발현임.

유전자 염기서열이 바뀐다는 것은 침팬치가 인간이 될 수 있다는 것과 같은 의미이므로 바뀌는데는 많은시간(몇 백만년)이 필요함. 

인간의 식생활에 중요한 변화

1) 1만년전 인류가 농사를 짓기 시작하면서 벼, 밀같은 곡물을 먹기 시작하였고 야생동물이 아니라 가축을 먹기 시작함. 

2) 2차 세계대전 이후 농약, 화학비료등 화학첨가물이 첨가된 음식을 먹기 시작함. 

에스키모인, 마사이부족 등은 에너지의 80-90%를 동물성 지방과 단백질에서 얻은 부족임. 그들이 도시로 이주하여 채식, 탄수화물을 먹는다면 건강할까? 

• Original Communication
• Published: 18 March 2002

The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic

• L Cordain, 
• SB Eaton, 
• J Brand Miller, 
• N Mann & 
• K Hill 

European Journal of Clinical Nutrition volume 56, pagesS42–S52(2002)Cite this article

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Abstract

Objective: Field studies of twentieth century hunter-gathers (HG) showed them to be generally free of the signs and symptoms of cardiovascular disease (CVD). Consequently, the characterization of HG diets may have important implications in designing therapeutic diets that reduce the risk for CVD in Westernized societies. Based upon limited ethnographic data (n=58 HG societies) and a single quantitative dietary study, it has been commonly inferred that gathered plant foods provided the dominant energy source in HG diets.

Method and Results: In this review we have analyzed the 13 known quantitative dietary studies of HG and demonstrate that animal food actually provided the dominant (65%) energy source, while gathered plant foods comprised the remainder (35%). This data is consistent with a more recent, comprehensive review of the entire ethnographic data (n=229 HG societies) that showed the mean subsistence dependence upon gathered plant foods was 32%, whereas it was 68% for animal foods. Other evidence, including isotopic analyses of Paleolithic hominid collagen tissue, reductions in hominid gut size, low activity levels of certain enzymes, and optimal foraging data all point toward a long history of meat-based diets in our species. Because increasing meat consumption in Western diets is frequently associated with increased risk for CVD mortality, it is seemingly paradoxical that HG societies, who consume the majority of their energy from animal food, have been shown to be relatively free of the signs and symptoms of CVD.

Conclusion: The high reliance upon animal-based foods would not have necessarily elicited unfavorable blood lipid profiles because of the hypolipidemic effects of high dietary protein (19–35% energy) and the relatively low level of dietary carbohydrate (22–40% energy). Although fat intake (28–58% energy) would have been similar to or higher than that found in Western diets, it is likely that important qualitative differences in fat intake, including relatively high levels of MUFA and PUFA and a lower ω-6/ω-3 fatty acid ratio, would have served to inhibit the development of CVD. Other dietary characteristics including high intakes of antioxidants, fiber, vitamins and phytochemicals along with a low salt intake may have operated synergistically with lifestyle characteristics (more exercise, less stress and no smoking) to further deter the development of CVD.

장내미생물(프로바이오틱스) 이야기

장내미생물은 보이지 않는 장기로서 인체의 하나의 중요한 기관임. 그런데 보통 연구자들은 장내 미생물을 우리 몸에 좋은 미생물과 나쁜 미생물로 나눠놓고 좋은 미생물이 장내에 살면 우리 면역체계도 튼튼해지고 건강해진다고 이야기함. 지금도 연구자들은 열심히 편가르기를 해서 좋은 균으로 밝혀지면 집중 배양해서 캡슐에 수억마리씩 넣어 우리 몸에 집어 넣을 궁리를 함. 

모든 생명체 서식의 기본은 먹이의 존재에 따라서 결정됨. 바퀴벌레가 많은 곳에는 바퀴벌레가 좋아하는먹이가 많기 때문임. 미생물도 마찬가지여서 수억마리, 수조마리를 집어넣어 줘도 먹이가 없으면 밑빠진독에 물붙기임. 좋은 미생물이 좋아하는 먹이가 바로 식물성 식품에 가득 들어있는 식이섬유임. 

그리고 먹는 것 외에도 장내미생물에 영향을 미치는 중요한 요소가 있는데 바로 POPs임. 2005년 경 처음 POPs라는 물질의 실체을 알고나서 의학자의 한사람으로서 참으로 공포스러웠음. 그렇게나 분해가 안되는 독한 화학물질이 지구상의 온 먹이사슬을 다 오염시켰다니 정말 인류는 이제 끝이구나라는 절망감에 우울증에 빠져있었음. 어느날 생물학적 환경정화(bioremediation)라고 토양이 화학물질로 극심하게 오염되었을때 미생물을 이용하여 오염물질을 분해하는 연구임. 이중 아키아(archaea)는 토양을 오염시킨POPs물질을 분해함. 

Archaea in Wastewater Treatment: Current Research and Emerging Technology

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Review Article | Open Access

Volume 2018 |Article ID 3194108 | 17 pages | https://doi.org/10.1155/2018/3194108

Diversity and Niche of Archaea in Bioremediation

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Mark James Krzmarzick,¹ David Kyle Taylor,¹ Xiang Fu,¹ and Aubrey Lynn McCutchan¹

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Academic Editor: Yu Tao

Received05 May 2018

Accepted01 Aug 2018

Published03 Sep 2018

Abstract

Bioremediation is the use of microorganisms for the degradation or removal of contaminants. Most bioremediation research has focused on processes performed by the domain Bacteria; however, Archaea are known to play important roles in many situations. In extreme conditions, such as halophilic or acidophilic environments, Archaea are well suited for bioremediation. In other conditions, Archaea collaboratively work alongside Bacteria during biodegradation. In this review, the various roles that Archaea have in bioremediation is covered, including halophilic hydrocarbon degradation, acidophilic hydrocarbon degradation, hydrocarbon degradation in nonextreme environments such as soils and oceans, metal remediation, acid mine drainage, and dehalogenation. Research needs are addressed in these areas. Beyond bioremediation, these processes are important for wastewater treatment (particularly industrial wastewater treatment) and help in the understanding of the natural microbial ecology of several Archaea genera.

아키아 종류들은 흔히 생명체가 살 수 없다고 생각하는 곳에서 주로 번식함. 화산, 염도가 상상을 초월하는 짠물 등등. 아키아를 이용해서 토양의 POPs오염을 해결하듯이 인체의 POPs 오염문제를 해결하는 방법을  연구하던 중 비만한 사람의 장내에 아키아들이 많이 산다는 연구 논문을 보게됨. 이 아키아들이 왜비만을 일으키는지 분자생물학적 기전은 대충 밝혀져 있음. 그렇지만 이러한 사실은 보다 넓은 생태학적인 관점에서 이 장내 미생물의 문제를 바라보는 계기가 됨. 

Human gut microbiota in obesity and after gastric bypass

Husen Zhang, John K. DiBaise, [...], and Rosa Krajmalnik-Brown

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ABSTRACT

Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. 

Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H2-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H2-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H2-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H2-producing bacteria with relatively high numbers of H2-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H2 transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.

Keywords: methanogen, microbial community, syntrophy, pyrosequencing, microbiome

자연에서 청정토양과 기름에 오염된 토양을 비교하면 거기에 서식하는 미생물의 분포는 완전히 다름. 오염이 안된 청정토양이 사고로 기름에 오염되면 그 기름을 분해하여 먹고사는 미생물의 수가 폭발적으로 증가함. 그러면서 서서히 오염원이 분해되고 자연은 원래 상태로 되돌아감. 

똑같은 일이 우리 장내에서도 발생함. POPs라는 물질이 우리의 지방조직에 저장되어 있는 물질이지만 끊임없이 담즙을 통하여 그리고 대장의 점막을 통하여 우리의 소화관으로 쏟아져 나옴. 그러니까 이 POPs를 분해해서 먹고사는 미생물의 종류들이 우리 장내에 존재함. 아키아도 그중 하나임. 그래서 장내에 POPs 물질이 많으면 이들을 먹고사는 아키아 균이 증가하게 되는데 아키아의 중가는 다른 장내미생물의분포에 연쇄적으로 영향을 미치게 되고 전체적으로 장내 미생물이라는 거대한 생태계에 영향을 주게 되고 결국은 대장에서 미생물이 만들어내는 칼로리의 양이 증가하여 비만이 됨. 

Associations among Organochlorine Pesticides, Methanobacteriales, and Obesity in Korean Women

• Hae-Sook Lee,
• Je-Chul Lee,
• In-Kyu Lee,
• Hyo-Bang Moon,
• Yoon-Seok Chang,
• David R. Jacobs Jr,
• Duk-Hee Lee 

• Published: November 17, 2011
• https://doi.org/10.1371/journal.pone.0027773

Abstract

Background

Although Methanobacteriales in the gut has recently been linked to obesity, no study has examined the hypothesis that waist circumference, a marker of visceral obesity, are positively associated with Methanobacteriales in the general population. Since Methanobacterialesincrease in a petroleum-contaminated environment to biodegrade petroleum as one way of autopurification, we also hypothesized that high body burden of highly lipophilic petroleum-based chemicals like organochlorine pesticides (OCPs) is associated with higher levels of Methanobacteriales in the gut.

Methodology/Principal Findings

Among 83 Korean women who visited a community health service center for a routine health checkup, quantitative real-time PCR (qPCR) based on 16S rDNA was used to quantify Methanobacteriales in feces. Nine OCPs were measured in both serum and feces of 16 subjects. Methanobacteriales were detected in 32.5% (27/83 women). Both BMI and waist circumference among women with Methanobacteriales were significantly higher than in women without Methanobacteriales (P = 0.04 and P = 0.01, respectively). Also, Methanobacterialeslevels in feces were positively associated with BMI and waist circumference (r = +0.23 and P = 0.03 for both). Furthermore, there were significant correlations between feces Methanobacteriales levels and serum concentrations of most OCPs, including with cis-nonachlor (r = +0.53, P<0.05), oxychlordane (r = +0.46, P<0.1), and trans-nonachlor (r = +0.43, P<0.1). Despite high correlations of serum and feces concentrations of most OCPs, feces OCP concentrations were not clearly associated with feces Methanobacteriales levels.

Conclusion/Significance

In this cross-sectional study, the levels of Methanobacteriales in the human gut were associated with higher body weight and waist circumference. In addition, serum OCP concentrations were positively correlated with levels of Methanobacteriales. There may be a meaningful link among body burden of OCP, Methanobacteriales in the gut, and obesity in the general population.

그렇다면 아키아는 좋은 균일까요? 나쁜 균일까요? 

우리 장내로 들어오는 POPs를 가능한 빨리 몸밖으로배출하거나 분해를 해주어야 하는데 그런 측면에서 보면 좋은 균임. 비만의 입장에서 보면 나쁜 균임. 아키아균에게만 POPs의 분해를 맡겨두기 보다는 다른 방법을 찾아야 하는데 가장 좋은 방법은 식이섬유가풍부한 식물성 섬취를 대량으로 늘려야 함. 

소금 적게먹으면 좋은 것일까? 

소금에 대한 전문가들의 삼단논법은 다음과 같음. 

나트륨을 많이 먹으면 혈압이 올라감

혈압이 높으면 뇌졸중, 심장병의 위험어 올라감

그러므로 나트륨을 적게 먹으면 심혈관계 질환에 걸릴 위험이 줄어들 것임.

이 삼단논법의 최종결론인 소금섭취와 심혈관계 질환 발생간의 관련성은 모호함. 

2011년 JAMA논문

Original Contribution 

November 23/30, 2011

Urinary Sodium and Potassium Excretion and Risk of Cardiovascular Events

Martin J. O'Donnell, MB, PhD; Salim Yusuf, DPhil, FRCPC, FRSC; Andrew Mente, PhD; et alPeggy Gao, MSc; Johannes F. Mann, MD; Koon Teo, MB, PhD; Matthew McQueen, MD; Peter Sleight, MD; Arya M. Sharma, MD; Antonio Dans, MD; Jeffrey Probstfield, MD; Roland E. Schmieder, MD

Author Affiliations Article Information

JAMA. 2011;306(20):2229-2238. doi:10.1001/jama.2011.1729

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Urinary Sodium and Potassium Excretion and Risk of Cardiovascular Events

Abstract

Context The precise relationship between sodium and potassium intake and cardiovascular (CV) risk remains uncertain, especially in patients with CV disease.

Objective To determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and CV events in patients with established CV disease or diabetes mellitus.

Design, Setting, and Patients Observational analyses of 2 cohorts (N = 28 880) included in the ONTARGET and TRANSCEND trials (November 2001-March 2008 from initial recruitment to final follow-up). We estimated 24-hour urinary sodium and potassium excretion from a morning fasting urine sample (Kawasaki formula). We used restricted cubic spline plots to describe the association between sodium and potassium excretion and CV events and mortality, and to identify reference categories for sodium and potassium excretion. We used Cox proportional hazards multivariable models to determine the association of urinary sodium and potassium with CV events and mortality.

Main Outcome Measures CV death, myocardial infarction (MI), stroke, and hospitalization for congestive heart failure (CHF).

Results At baseline, the mean (SD) estimated 24-hour excretion for sodium was 4.77 g (1.61); and for potassium was 2.19 g (0.57). After a median follow-up of 56 months, the composite outcome occurred in 4729 (16.4%) participants, including 2057 CV deaths, 1412 with MI, 1282 with stroke, and 1213 with hospitalization for CHF. Compared with the reference group with estimated baseline sodium excretion of 4 to 5.99 g per day (n = 14 156; 6.3% participants with CV death, 4.6% with MI, 4.2% with stroke, and 3.8% admitted to hospital with CHF), higher baseline sodium excretion was associated with an increased risk of CV death (9.7% for 7-8 g/day; hazard ratio [HR], 1.53; 95% CI, 1.26-1.86; and 11.2% for >8 g/day; HR, 1.66; 95% CI, 1.31-2.10), MI (6.8%; HR, 1.48; 95% CI, 1.11-1.98 for >8 g/day), stroke (6.6%; HR, 1.48; 95% CI, 1.09-2.01 for >8 g/day), and hospitalization for CHF (6.5%; HR, 1.51; 1.12-2.05 for >8 g/day). Lower sodium excretion was associated with an increased risk of CV death (8.6%; HR, 1.19; 95% CI, 1.02-1.39 for 2-2.99 g/day; 10.6%; HR, 1.37; 95% CI, 1.09-1.73 for <2 g/day), and hospitalization for CHF (5.2%; HR, 1.23; 95% CI, 1.01-1.49 for 2-2.99 g/day) on multivariable analysis. Compared with an estimated potassium excretion of less than 1.5 g per day (n = 2194; 6.2% with stroke), higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/day; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/day; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/day; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for >3 g/day) on multivariable analysis.

Conclusions The association between estimated sodium excretion and CV events was J-shaped. Compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all CV events, and a sodium excretion of less than 3 g per day was associated with increased risk of CV mortality and hospitalization for CHF. Higher estimated potassium excretion was associated with a reduced risk of stroke.

오메가 3, 오메가 6

원래 1:1이어야 하는데 현대인은 오메가 6를 과다하게 복용하므로 오메가 3가 중요해짐. 

모유와 POPs

2002년 Lancet에  모유를 1년이상 먹은 아이가 9-26세가 될때까지 장기추적한 결과 아토피, 천식과 같은 알레르기가 더 많이 발생했다는 논문. 

sears2002.pdf

Long-term Relation Between Breastfeeding and Development of Atopy and Asthma in Children and Young Adults: A Longitudinal Study

Malcolm R Sears 1, Justina M Greene, Andrew R Willan, D Robin Taylor, Erin M Flannery, Jan O Cowan, G Peter Herbison, Richie Poulton

Affiliations expand

• PMID: 12354471
 
• DOI: 10.1016/S0140-6736(02)11025-7

Abstract

Background: Breastfeeding is widely advocated to reduce risk of atopy and asthma, but the evidence for such an effect is conflicting. We aimed to assess long-term outcomes of asthma and atopy related to breastfeeding in a New Zealand birth cohort.

Methods: Our cohort consisted of 1037 of 1139 children born in Dunedin, New Zealand, between April, 1972, and March, 1973, and residing in Otago province at age 3 years. Children were assessed every 2-5 years from ages 9 to 26 years with respiratory questionnaires, pulmonary function, bronchial challenge, and allergy skin tests. History of breastfeeding had been independently recorded in early childhood.

Findings: 504 (49%) of 1037 eligible children were breastfed (4 weeks or longer) and 533 (51%) were not. More children who were breastfed were atopic at all ages from 13 to 21 years to cats (p=0.0001), house dust mites (p=0.0010), and grass pollen (p<0.0001) than those who were not. More children who were breastfed reported current asthma at each assessment between age 9 (p=0.0008) and 26 years (p=0.0008) than those who were not. Breastfeeding effects were not affected by parental history of hayfever or asthma. Multifactor analysis controlling for socioeconomic status, parental smoking, birth order, and use of sheepskin bedding in infancy, showed odds ratios of 1.94 (95% CI 1.42-2.65, p<0.0001) for any allergen positive at age 13 years, 2.40 (1.36-4.26, p=0.0003) for current asthma at 9 years, and 1.83 (1.35-2.47, p<0.0001) for current asthma at 9-26 years by repeated-measures analysis.

일반적으로 모유수유를 하면 알레르기 질환이 줄어든다는 연구가 많음. 

과연 모유는 알레르기성 질환과 어떤 관련이 있을까? 

모유와 알레르기 질환간의 연관성이 연령대에 따라 다르게 나타남. 모유가 가진 장점은 즉각적이고 어릴수록 더 또렷하게 나타나고 모유를 오염시킨 화학물질간의 문제점은 아이들이 커감에 따라 서서히 나타날 가능성이 높음. 

현대사회는 POPs를 피할 수 없는 시대임. 그래서 POPs 배출에 더 신경써야 함. 

지용성이 높은 화학물질의 혼합체가 가능한한 모유로 가는 것을 막는 방법

1) 모유수유기간동안에 빨리 출산전의 몸매로 돌아가면 안됨. 지방에 저장된 POPs가 혈액에 노출되고 모유를 통해 아이에 전달되기 때문

2) 임신과 수유기에는 현미밥, 과일채소를 껍질채 매끼니마다 먹기. 식이섬유와 파이토케미컬은 엄마 몸에 들어와있는 POPs를 배출함. 

3) 동물성 식품을 먹을때는(POPs는 동물성 식품의 지방에 저장되어 있음) 가능한 기름이 없는 부위를 선택, 내장부위는 피하고 뜨거운물에 데쳐서 먹는 것을 권유함

4) 운동으로 POPs 배출량을 늘림

우유를 어떻게 볼것인가? 

2014년 우유를 먹은 사람들에 대한 대규모 추적조사 결과 우유를 많이 마신 사람들이 심장병이나 암으로 죽을 위험성이 높고 골다공증 위험성이 더 높다는 논문. 

Milk intake and risk of mortality and fractures in women and men: cohort studies

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g6015 (Published 28 October 2014)Cite this as: BMJ 2014;349:g6015 

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1. Karl Michaëlsson, professor1,  
2. Alicja Wolk, professor2,  
3. Sophie Langenskiöld, senior lecturer3,  
4. Samar Basu, professor3,  
5. Eva Warensjö Lemming, researcher14,  
6. Håkan Melhus, professor5,  
7. Liisa Byberg, associate professor1

Author affiliations

1. Correspondence to: K Michaëlsson karl.michaelsson@surgsci.uu.se

• Accepted 22 September 2014

Abstract

Objective To examine whether high milk consumption is associated with mortality and fractures in women and men.

Design Cohort studies.

Setting Three counties in central Sweden.

Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.

Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.

Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).

Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.

2013년 인간이 어떻게 우유에 적응해왔는지 고고학적으로 설명한 논문. 

이 논문에서는 전세계 성인 인구의 약 1/3 정도는 우유 소화효소를 진화과정에서 습득했음. 

하지만 늘 이야기하듯이 21세기 식품 속에 들어있는 영양소만 가지고 그 식품을 이야기하는 것은 절반의진실임. 

MSG이야기

MSG는 물에 잘 녹고 기름에 녹지 않는 특성을 가진 POPs와 정반대의 성격을 가진 화학물질임. 그래서 체외 배설이 잘됨. 반감기는 30분정도임.  MSG가 많이 든 음식을 먹으면 불편한 사람은 복용하지 않는 것이 좋음. MSG를 먹어도 아무 느낌이 없는 사람들은 MSG보다 더 문제가 많은 화학물질은 세상에 널려있으므로 고민없이 살아도 될듯함.