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明胶、压力、长寿

**Gelatin, stress, longevity**

放弃空心树旅客 今天

Gelatin, stress, longevity

明胶、压力、长寿

by Raymond Peat 

The main bulk of an animal's body consists of water, protein, fat and bones. Fat tissue and bone are metabolically more quiescent than the protein-water systems. During stress or starvation, or even hibernation, animals lose lean mass faster than fat.

The amino acids that constitute protein have many hormone-like functions in their free state. When our glucose (glycogen) stores have been depleted, we convert our own tissue into free amino acids, some of which are used to produce new glucose. The amino acids cysteine and tryptophan, released in large quantities during stress, have antimetabolic (thyroid-suppressing) and, eventually, toxic effects. 

Hypothyroidism itself increases the catabolic turnover of protein, even though general metabolism is slowed.

Other amino acids act as nerve-modifiers (“transmitters”), causing, for example, excitation or inhibition.

动物身体的主要部分由水、蛋白质、脂肪和骨骼组成。脂肪组织和骨骼在代谢上比蛋白质-水系统更安静。在压力或饥饿,甚至冬眠期间,动物瘦肉的损失比脂肪的损失要快。

组成蛋白质的氨基酸在其自由状态下具有许多类似激素的功能。当我们体内储存的葡萄糖(糖原)被耗尽时,我们就会将自己的组织转化为游离氨基酸,其中一些氨基酸被用来产生新的葡萄糖。在压力下大量释放的氨基酸半胱氨酸和色氨酸具有抗代谢(甲状腺抑制)作用,最终产生毒性作用。

甲状腺机能减退会增加蛋白质的分解代谢,尽管一般代谢会减慢。

其他氨基酸作为神经调节剂(“递质”),例如引起兴奋或抑制。

Some of these amino acids, such as glycine, have a very broad range of cell-protective actions.

Their physical properties, rather than their use for production of energy or other metabolic function, are responsible for their important cytoprotective actions.

Gelatin (the cooked form of collagen) makes up about 50% of the protein in an animal, but a much smaller percentage in the more active tissues, such as brain, muscle, and liver. 35% of the amino acids in gelatin are glycine, 11% alanine, and 21% proline and hydroxyproline.

In the industrialized societies, the consumption of gelatin has decreased, relative to the foods that contain an inappropriately high proportion of the antimetabolic amino acids, especially tryptophan and cysteine.

The degenerative and inflammatory diseases can often be corrected by the use of gelatin-rich foods.

其中一些氨基酸,如甘氨酸,具有非常广泛的细胞保护作用。

它们的物理特性,而不是它们用于生产能量或其他代谢功能,是它们重要的细胞保护作用的原因。

明胶(煮熟的胶原蛋白)约占动物蛋白质的50%,但在大脑、肌肉和肝脏等更活跃的组织中,这个比例要小得多。明胶中35%的氨基酸为甘氨酸,11%为丙氨酸,21%为脯氨酸和羟脯氨酸。

在工业化社会中,相对于含有过高比例的抗代谢氨基酸,特别是色氨酸和半胱氨酸的食物,明胶的消费量已经减少。

退行性和炎性疾病通常可以通过食用富含明胶的食物来纠正。

I usually think about something for a long time before I get around to integrating it into my life, sometimes because old habits have to be changed, but usually because our social organization is set up to do things in conventional ways. Our foods reflect our social organization, enforced by laws and rules. When I first went to Mexico to study, many traditional foods were still available even in the city–fried pig skin, served crisp or boiled with a sauce, blood tacos, cartilaginous parts of various animals, chicken-foot soup, crustaceans, insects, etc. Later, when I studied biochemistry, I realized that each part of an organism has a characteristic chemistry and special nutritional value. I knew of Weston Price's research on traditional diets, and his argument that the degenerative “diseases of civilization” were produced by the simplified diets that are characteristic of the highly industrialized societies.

As I began to study endocrinology, I realized that there were some radical misconceptions behind the ideas of “scientific nutrition.” I. P. Pavlov, who had studied nutritional physiology because it constituted the animal's closest interactions with its environment, was motivated by a desire to understand life in its totality, including consciousness. But western nutritionists were nearly all committed to an ideology that forced them to think in terms of “essential factors for growth,” leading to ideas such as “minimum daily requirement” for each nutrient. Bodily bulk (especially body length) was the criterion, not the experienced quality of life. And there has been no scarcity of evidence showing that rapid bodily growth has its drawbacks (e.g., Miller, et al., 2002, “Big mice die young”).

One of the brightest of the genetically oriented nutritionists, Roger Williams, used the idea of genetic individuality to explain that the popular idea of a species-wide standard diet couldn't be applied to exceptional individuals, and that disease was often the result of the mismatch between special nutritional requirements and a “standard” diet. Linus Pauling's concept of orthomolecular medicine was a restatement of Williams' principle for the general scientific community.

我通常会花很长时间思考一件事,然后才把它融入我的生活,有时是因为旧的习惯需要改变,但通常是因为我们的社会组织是按照传统方式来做事情的。我们的食物反映了我们的社会组织,由法律和规则执行。当我第一次去墨西哥学习的时候,即使在城市里,许多传统食物仍然可以买到——炸猪皮、松脆的或用酱汁煮的猪皮、血玉米饼、各种动物的软骨部分、鸡脚汤、甲壳类动物、昆虫等等。后来,当我学习生物化学时,我意识到一个有机体的每个部分都有其特有的化学和特殊的营养价值。我知道韦斯顿·普莱斯(Weston Price)对传统饮食的研究,以及他的观点,即退化的“文明疾病”是由高度工业化社会特有的简化饮食造成的。

当我开始学习内分泌学时,我意识到在“科学营养”的概念背后存在着一些根本性的误解。巴甫洛夫之所以研究营养生理学,是因为它构成了动物与环境之间最密切的相互作用。他的动机是想从整体上理解生命,包括意识。但西方营养学家几乎都信奉一种意识形态,迫使他们从“生长的必要因素”的角度来思考,从而得出诸如每种营养的“每日最低需求量”之类的观点。体型(尤其是体长)是衡量标准,而不是生活质量。而且,没有足够的证据表明身体快速生长有其缺点(例如,Miller等人,2002年,“大老鼠死得早”)。

面向基因的一个最聪明的营养学家,罗杰·威廉姆斯,使用遗传个性的概念来解释的流行观点,各种标准饮食不能适用于特殊的个体,这疾病往往是不匹配的结果之间的特殊营养需求和“标准”的饮食。莱纳斯·鲍林关于正分子医学的概念是威廉姆斯原则在科学界的重述。

But still, the emphasis was on the match between a specific chemical and the genetic constitution of the organism. Pavlov's idea of the “trophic” actions of nerves was discarded, and the rest of his work was relegated to a crudely caricatured branch of psychology. His therapeutic recommendation of beef broth for many ailments was ignored as having nothing to do with the caricatured “Pavlovism.”

If nerves are intimately involved in the processes of nutrition and development, the effects of nutrients on the nerves and their development should have a central place in nutritional research. Our appetites reflect our biochemical needs, and our “unconditional reflexes” are likely to be wiser than the theories that are based simply on the amount of weight a young animal gains on a particular diet.

When I began teaching endocrinology, some of my students didn't want to hear about anything except “lock and key” endocrinology, in which “a hormone” signals certain cells that have a suitable receptor for that hormone. But the studies of Hans Selye and Albert Szent-Gyorgyi made it clear that Pavlov's global, holistic approach to the organism in its environment was the soundest scientific basis for physiology, including endocrinology. A cell's response to a hormone depended on the state of the cell. Nutrients and metabolites and hormones and neurotransmitters all modify the cell's sensitivity to its surroundings. The assumptions of “molecular biology,” as generally understood, are fundamentally mistaken.

The idea of fixed requirements for specific nutrients, and especially the idea that rapid physical growth was the way to determine the essentiality of a substance, led to a monstrous distortion of the official dietary recommendations. Business, industry, government, and the health professions collaborated in the propagation of an ideology about nutrition that misrepresented the nature of the living organism.

但是,重点仍然是特定的化学物质和生物体的遗传结构之间的匹配。巴甫洛夫关于神经的“营养”作用的观点被抛弃了,他的其他工作也被贬为心理学的一个粗俗的分支。他建议用牛肉汤治疗许多疾病,但被忽视了,因为这与漫画中的“巴甫洛夫主义”毫无关系。

如果神经与营养和发育的过程密切相关,那么营养对神经及其发育的影响应该在营养研究中占有中心地位。我们的食欲反映了我们的生化需求,我们的“无条件反射”可能比那些仅仅基于幼小动物在特定饮食中增加的体重的理论更明智。

当我开始教内分泌学的时候,我的一些学生除了“锁和钥匙”内分泌学以外,什么都不想听。但是Hans Selye和Albert Szent-Gyorgyi的研究表明,巴甫洛夫对环境中的有机体的全面、整体的研究方法是生理学(包括内分泌学)最可靠的科学基础。细胞对激素的反应取决于细胞的状态。营养物质、代谢物、激素和神经递质都改变了细胞对周围环境的敏感性。一般认为,“分子生物学”的假设从根本上是错误的。

人们对特定营养物质的需求是固定不变的,特别是认为快速的身体生长是确定一种物质的本质的方法,这导致了对官方饮食建议的巨大扭曲。商业、工业、政府和健康专业人士合作传播了一种关于营养的意识形态,这种意识形态歪曲了生命有机体的本质。

Most studies of the nutritional requirements for protein have been done for the agricultural industries, and so have been designed to find the cheapest way to get the maximum growth in the shortest time. The industry isn't interested in the longevity, intelligence, or happiness of their pigs, chickens, and lambs. The industry has used chemical growth stimulants in combination with the foods that support rapid growth at least expense. Antibiotics and arsenic and polyunsaturated fatty acids have become part of our national food supply because they produce rapid weight gain in young animals.

The amino acids in proteins have been defined as “essential” on the basis of their contribution to growth, ignoring their role in producing long life, good brain development, and good health. The amino acid and protein requirements during aging have hardly been studied, except in rats, whose short life-span makes such studies fairly easy. The few studies that have been done indicate that the requirements for tryptophan and cysteine become very low in adulthood.

Although Clive McKay's studies of life extension through caloric restriction were done in the 1930s, only a few studies have been done to find out which nutrients' restriction contributes most to extending the life span. Restricting toxic heavy metals, without restricting calories, produces about the same life-extending effect as caloric restriction. Restricting only tryptophan, or only cysteine, produces a greater extension of the life span than achieved in most of the studies of caloric restriction. How great would be the life-span extension if both tryptophan and cysteine were restricted at the same time?

Both tryptophan and cysteine inhibit thyroid function and mitochondrial energy production, and have other effects that decrease the ability to withstand stress. Tryptophan is the precursor to serotonin, which causes inflammation, immunodepression, and generally the same changes seen in aging. Histidine is another amino acid precursor to a mediator of inflammation, histamine; would the restriction of histidine in the diet have a longevity promoting effect, too?

大多数关于蛋白质营养需求的研究都是针对农业工业进行的,因此研究的目的是寻找最便宜的方法,在最短的时间内获得最大的增长。这个行业对他们的猪、鸡、羊的寿命、智力或幸福不感兴趣。该行业已经将化学生长刺激剂与支持快速生长的食品结合使用,至少成本较高。抗生素、砷和多不饱和脂肪酸已经成为我国食品供应的一部分,因为它们会使幼龄动物体重快速增加。

蛋白质中的氨基酸被定义为“必需的”,这是基于它们对生长的贡献,而忽略了它们在长寿、大脑发育和健康方面的作用。除了老鼠,几乎没有人研究过衰老过程中对氨基酸和蛋白质的需求,因为老鼠的寿命很短,所以这样的研究相当容易。少数已经完成的研究表明,色氨酸和半胱氨酸的需求在成年期变得非常低。

尽管克莱夫·麦凯(Clive McKay)通过限制热量延长寿命的研究是在20世纪30年代完成的,但只有少数研究发现限制哪些营养物质对延长寿命的作用最大。在不限制卡路里的情况下,限制有毒重金属的摄入,产生的延长寿命的效果与限制卡路里摄入差不多。只限制色氨酸,或只限制半胱氨酸,比大多数热量限制的研究更能延长寿命。如果同时限制色氨酸和半胱氨酸,寿命会有多大的延长?

色氨酸和半胱氨酸都抑制甲状腺功能和线粒体能量的产生,并有其他降低承受压力的能力的作用。色氨酸是5 -羟色胺的前体,5 -羟色胺会导致炎症、免疫抑制,以及通常在衰老过程中看到的相同变化。组氨酸是另一种氨基酸前体,是炎症的中介物,组胺;饮食中限制组氨酸的摄入也会有促进长寿的效果吗?

It happens that gelatin is a protein which contains no tryptophan, and only small amounts of cysteine, methionine, and histidine. Using gelatin as a major dietary protein is an easy way to restrict the amino acids that are associated with many of the problems of aging.

The main amino acids in gelatin are glycine and proline; alanine is also present in significant quantity. Glycine and proline are responsible for the unusual fibrous property of collagen.

An animal's body, apart from fat and water, is mostly protein, and about half of the protein in the body is collagen (which is the native, uncooked form of gelatin). Its name is derived from its traditional use as glue. It is responsible for the structural toughness of mature animal bodies.

When cells are stressed, they form extra collagen, but they can also dissolve it, to allow for tissue remodeling and growth. Invasive cancers over-produce this kind of enzyme, destroying the extracellular matrix which is needed for normal cellular differentiation and function. When collagen is broken down, it releases factors that promote wound healing and suppress tumor invasiveness. (Pasco, et al., 2003) Glycine itself is one of the factors promoting wound healing and tumor inhibition.

明胶是一种不含色氨酸的蛋白质,只含有少量的半胱氨酸、蛋氨酸和组氨酸。使用明胶作为主要的膳食蛋白质是一种简单的方法来限制与许多老化问题有关的氨基酸。

明胶中的主要氨基酸有甘氨酸和脯氨酸;丙氨酸也大量存在。甘氨酸和脯氨酸是胶原蛋白不同寻常的纤维性质的原因。

动物的身体,除了脂肪和水,主要是蛋白质,体内大约一半的蛋白质是胶原蛋白(这是天然的、未煮熟的明胶形式)。它的名字来源于它作为胶水的传统用途。它决定了成熟动物身体的结构韧性。

当细胞受到压力时,它们会形成额外的胶原蛋白,但它们也可以溶解胶原蛋白,以允许组织重塑和生长。侵袭性癌症会过度产生这种酶,破坏正常细胞分化和功能所需的细胞外基质。当胶原蛋白被分解时,它会释放促进伤口愈合和抑制肿瘤侵袭的因子。(Pasco, et al., 2003)甘氨酸本身就是促进伤口愈合和抑制肿瘤的因素之一。

It has a wide range of antitumor actions, including the inhibition of new blood vessel formation (angiogenesis), and it has shown protective activity in liver cancer and melanoma. Since glycine is non-toxic (if the kidneys are working, since any amino acid will contribute to the production of ammonia), this kind of chemotherapy can be pleasant.

When we eat animal proteins in the traditional ways (for example, eating fish head soup, as well as the muscles, or “head-cheese” as well as pork chops, and chicken-foot soup as well as drumsticks), we assimilate a large amount of glycine and gelatin. This whole-animal balance of amino acids supports all sorts of biological process, including a balanced growth of children's tissues and organs.

When only the muscle meats are eaten, the amino acid balance entering our blood stream is the same as that produced by extreme stress, when cortisol excess causes our muscles to be broken down to provide energy and material for repair. The formation of serotonin is increased by the excess tryptophan in muscle, and serotonin stimulates the formation of more cortisol, while the tryptophan itself, along with the excess muscle-derived cysteine, suppresses the thyroid function.

它具有广泛的抗肿瘤作用,包括抑制新血管形成(血管生成),并在肝癌和黑色素瘤中显示出保护作用。因为甘氨酸是无毒的(如果肾脏正常工作,因为任何氨基酸都会促进氨的产生),这种化疗是令人愉快的。

当我们以传统的方式吃动物蛋白时(例如,吃鱼头汤,还有肌肉,或者“头奶酪”,还有猪排,鸡脚汤和鸡腿),我们吸收了大量的甘氨酸和明胶。这种氨基酸的全动物平衡支持各种生物过程,包括儿童组织和器官的平衡生长。

当只吃肌肉肉时,进入我们血液中的氨基酸平衡与在极端压力下产生的氨基酸平衡是一样的,皮质醇过量导致我们的肌肉被分解,以提供能量和修复所需的物质。肌肉中过量的色氨酸增加了血清素的形成,而血清素刺激更多的皮质醇的形成,而色氨酸本身,以及过量的肌肉衍生的半胱氨酸,抑制了甲状腺功能。

A generous supply of glycine/gelatin, against a balanced background of amino acids, has a great variety of antistress actions. Glycine is recognized as an “inhibitory” neurotransmitter, and promotes natural sleep. Used as a supplement, it has helped to promote recovery from strokes and seizures, and to improve learning and memory. But in every type of cell, it apparently has the same kind of quieting, protective antistress action. The range of injuries produced by an excess of tryptophan and serotonin seems to be prevented or corrected by a generous supply of glycine. Fibrosis, free radical damage, inflammation, cell death from ATP depletion or calcium overload, mitochondrial damage, diabetes, etc., can be prevented or alleviated by glycine.

Some types of cell damage are prevented almost as well by alanine and proline as by glycine, so the use of gelatin, rather than glycine, is preferable, especially when the gelatin is associated with its normal biochemicals. For example, skin is a rich source of steroid hormones, and cartilage contains “Mead acid,” which is itself antiinflammatory.

The other well-studied inhibitory neurotransmitter is GABA, so it's significant that GABA (gamma amino butyric acid) is a close analog of glycine (alpha amino acetic acid). A synthetic molecule structurally similar to those natural inhibitory “transmitters,” beta amino propanoic acid, has some of the protective effects of glycine and GABA. The other molecules in the series, at least up to epsilon amino caproic acid, have some of the same antiinvasive, antiinflammatory, anti-angiogenic, properties. Alanine and proline, with cell-protecting actions, have the same basic composition, carbon (CH2 or CH) atoms separating acid and amino groups. Even the amino acids in which the lipophilic carbon atoms extend out in a branched side-chain, valine, leucine, and isoleucine, have some of the antiseizure (inhibitory) action (Skeie, et al., 1992, 1994) of GABA and glycine. Tests done with one, or a few, of the relatively lipophilic (aliphatic) amino acids prevent seizures, while the “balanced” mixtures of amino acids permit seizures; unfortunately, results of this sort haven't led researchers to question the idea of “balance” that developed within the setting of agricultural research.

大量供应甘氨酸/明胶,在氨基酸平衡的背景下,有各种各样的抗应激作用。甘氨酸被认为是一种“抑制性”神经递质,能促进自然睡眠。作为一种补充剂,它有助于促进中风和癫痫的恢复,并改善学习和记忆。但在每一种细胞中,它显然都有相同的镇静、保护、抗应激作用。过量色氨酸和血清素所造成的一系列损伤似乎可以通过大量供应甘氨酸来预防或纠正。甘氨酸可预防或减轻纤维化、自由基损伤、炎症、ATP耗尽或钙超载引起的细胞死亡、线粒体损伤、糖尿病等。

丙氨酸和脯氨酸几乎与甘氨酸一样能防止某些类型的细胞损伤,所以使用明胶比使用甘氨酸更可取,特别是当明胶与它的正常生物化学物质相结合时。例如,皮肤是类固醇激素的丰富来源,软骨含有“米德酸”,它本身就是抗炎的。

另一种被广泛研究的抑制性神经递质是GABA,因此GABA(伽马氨基丁酸)是甘氨酸(α氨基乙酸)的类似物是很重要的。一种合成分子在结构上类似于那些天然的抑制性“递质”-氨基丙酸,具有甘氨酸和氨基丁酸的一些保护作用。该系列中的其他分子,至少达到氨基己酸,具有一些相同的抗侵袭、抗炎、抗血管生成的特性。丙氨酸和脯氨酸具有保护细胞的作用,它们具有相同的基本组成,即分离酸和氨基的碳原子(CH2或CH)。即使是亲脂碳原子在支链上延伸的氨基酸,缬氨酸、亮氨酸和异亮氨酸,也具有GABA和甘氨酸的一些抗癫痫(抑制)作用(Skeie等,1992,1994)。用一种或几种相对亲脂性(脂肪族)氨基酸进行的测试可以防止癫痫发作,而“平衡的”氨基酸混合物则允许癫痫发作;不幸的是,这类结果并没有让研究人员质疑在农业研究中形成的“平衡”概念。

The similarity between the structures and actions of glycine and GABA suggest that their “receptors” are similar, if not identical. For years, it has been known that progesterone and pregnenolone act on the GABA receptor, to reinforce the protective, inhibitory effects of GABA. Estrogen has the opposite effect, inhibiting GABA's action. Since GABA opposes estrogen and inhibits the growth of breast cancer, it wouldn't be surprising if glycine, alanine, etc., did the same.

Recent research shows that progesterone and its metabolites also act on the “glycine receptor,” increasing inhibition, and that the “phytoestrogen,” genistein, antagonizes the inhibitory effect of glycine.

The inhibitory systems are opposed by excitatory systems, especially by the excitatory amino acid system, activated by glutamic and aspartic acid. Progesterone and estrogen act on that system, too, decreasing and increasing excitation, respectively.

甘氨酸和GABA的结构和作用之间的相似性表明它们的“受体”是相似的,如果不是完全相同的话。多年来,人们已经知道孕酮和孕烯醇酮作用于GABA受体,以加强GABA的保护和抑制作用。雌激素有相反的作用,抑制GABA的作用。由于GABA反对雌激素并抑制乳腺癌的增长,所以如果甘氨酸、丙氨酸等也有同样的作用就不足为奇了。

最近的研究表明,孕酮及其代谢物也作用于“甘氨酸受体”,增加抑制,而“植物雌激素”染料木素,拮抗甘氨酸的抑制作用。

抑制系统与兴奋系统相反,特别是由谷氨酸和天冬氨酸激活的兴奋性氨基酸系统。黄体酮和雌激素也对该系统起作用,分别降低和增加兴奋。

I have previously discussed the arguments for viewing progesterone as a “cardinal adsorbent” (as in Ling and Fu, 1987, 1988, Ling, et al., 1984, a steroid alters glycine's influence on the cell's electrical behavior) which increases the lipophilic, fat-loving property of the cytoplasm, and estrogen as having the opposite action, increasing the water-loving hydrophilic quality of the cytoplasm. If we think of the proteins known as the GABA and glycine receptors as having some regions in which the basic amine of lysine associates with the acidic group of aspartic or glutamic acid, then the action of glycine, or other amino acids would be to introduce additional lipophilic carbon atoms into those regions (with the amino acids' polar ends pairing with their opposites on the protein), where the cardinal adsorbents exert their influence.

Generally, biologists seem puzzled by such facts, because they don't fit into the “lock and key” model of molecular biology. But I think they make the organism easier to understand, since these constellations of facts illustrate simple and general physical principles. They suggest the idea that estrogen and progesterone and glycine, GABA, etc., will be active in any functioning cell, at a suitable concentration. It was this kind of thinking in terms of general physical principles that led Szent-Gyorgyi to investigate the effects of estrogen and progesterone on heart physiology. The old characterization of estrogen and progesterone as “sex” and “pregnancy” hormones acting on a few tissues through specific receptors never had a good basis in evidence, but the accumulated evidence has now made those ideas impossible for an informed person to accept. (Progesterone increases the heart's pumping efficiency, and estrogen is antagonistic, and can produce cardiac arrhythmia.)

In the context of the excitatory actions of estrogen, and the inhibitory action of glycine, it would be reasonable to think of glycine as one of the antiestrogenic substances. Another type of amino acid, taurine, is structurally similar to glycine (and to beta amino propanoic acid, and to GABA), and it can be thought of as antiestrogenic in this context. The specific kinds of excitation produced by estrogen that relate to reproduction occur against a background of very generalized cellular excitation, that includes increased sensitivity of sensory nerves, increased activity of motor nerves, changes in the EEG, and, if the estrogen effect is very high, epilepsy, tetany, or psychosis.

我以前讨论过将孕酮视为“主要吸附剂”的观点(如Ling和Fu, 1987, 1988, Ling等人,1984,类固醇改变甘氨酸对细胞电行为的影响),它增加细胞质的亲脂性、亲脂性,而雌激素具有相反的作用,增加细胞质的亲水亲水性。如果我们认为氨基丁酸和甘氨酸受体的蛋白质有一些区域赖氨酸的碱性胺与天冬氨酸或谷氨酸的酸性基团相结合,那么甘氨酸的作用,或者其他氨基酸会将额外的亲脂碳原子引入这些区域(氨基酸的极性端与蛋白质的极性端配对),在那里主要吸附剂发挥作用。

一般来说,生物学家似乎对这些事实感到困惑,因为它们不符合分子生物学的“锁和钥匙”模型。但我认为它们使有机体更容易理解,因为这些事实排列说明了简单而普遍的物理原理。他们认为雌激素、孕酮、甘氨酸、伽马氨基丁酸等在适当的浓度下会在任何功能细胞中活跃。正是这种基于一般物理原理的思考,促使圣乔伊研究雌激素和孕酮对心脏生理的影响。过去把雌激素和黄体酮描述为通过特定受体作用于少数组织的“性”激素和“妊娠”激素,这种描述从来没有很好的证据基础,但积累的证据现在使那些有知识的人不可能接受这些观点。(孕酮增加心脏的泵送效率,而雌激素具有拮抗作用,可产生心律失常。)

在雌激素的兴奋作用和甘氨酸的抑制作用的背景下,将甘氨酸视为抗雌激素物质是合理的。另一种氨基酸,牛磺酸,在结构上类似于甘氨酸(和-氨基丙酸,GABA),在这种情况下,它可以被认为是抗雌激素的。由雌激素产生的与生殖有关的特殊兴奋是在非常普遍的细胞兴奋的背景下发生的,包括感觉神经的敏感性增加,运动神经的活动增加,脑电图的变化,如果雌激素的作用非常大,还会导致癫痫、抽搐或精神病。

Glycine's inhibitory effects appear to oppose estrogen's actions generally, in sensory and motor nerves, in regulating angiogenesis, and in modulating the cytokines and “chemokines” that are involved in so many inflammatory and degenerative diseases, especially tumor necrosis factor (TNF), nitric oxide (NO), and prostaglandins. Exposure to estrogen early in life can affect the health in adulthood, and so can an early deficiency of glycine. The degenerative diseases can begin in the earliest years of life, but because aging, like growth, is a developmental process, it's never too late to start the corrective process.

One of estrogen's “excitatory” effects is to cause lipolysis, the release of fatty acids from storage fat; it directs the conversion of glucose into fat in the liver, so that the free fatty acids in the circulation remain chronically high under its influence. The free fatty acids inhibit the oxidation of glucose for energy, creating insulin resistance, the condition that normally increases with aging, and that can lead to hyperglycemia and “diabetes.”

Gelatin and glycine have recently been reported to facilitate the action of insulin in lowering blood sugar and alleviating diabetes. Gelatin has been used successfully to treat diabetes for over 100 years (A. Guerard, Ann Hygiene 36, 5, 1871; H. Brat, Deut. Med. Wochenschrift 28 (No. 2), 21, 1902). Glycine inhibits lipolysis (another antiexcitatory, “antiestrogenic” effect), and this in itself will make insulin more effective, and help to prevent hyperglycemia. (A gelatin-rich diet can also lower the serum triglycerides.) Since persistent lipolysis and insulin resistance, along with a generalized inflammatory state, are involved in a great variety of diseases, especially in the degenerative diseases, it's reasonable to consider using glycine/gelatin for almost any chronic problem. (Chicken foot soup has been used in several cultures for a variety of ailments; chicken foot powder has been advocated as a stimulant for spinal cord regeneration–Harry Robertson's method was stopped by the FDA).

甘氨酸的抑制作用似乎与雌激素在感觉和运动神经、调节血管生成、调节参与许多炎症和退行性疾病的细胞因子和“趋化因子”,特别是肿瘤坏死因子(TNF)、一氧化氮(NO)和前列腺素方面的作用相反。早期接触雌激素会影响成年后的健康,早期缺乏甘氨酸也会影响成年后的健康。退行性疾病可能在生命的最初几年就开始了,但因为衰老,就像生长一样,是一个发展的过程,开始矫正过程永远不会太晚。

雌激素的“兴奋”作用之一是引起脂肪分解,从储存的脂肪中释放脂肪酸;它引导葡萄糖在肝脏中转化为脂肪,使循环中的游离脂肪酸在它的影响下长期保持高水平。游离脂肪酸会抑制葡萄糖氧化提供能量,产生胰岛素抵抗,而胰岛素抵抗通常会随着年龄增长而增加,从而导致高血糖和“糖尿病”。

明胶和甘氨酸最近被报道促进胰岛素在降低血糖和缓解糖尿病的作用。明胶被成功用于治疗糖尿病已有100多年的历史(A. Guerard, Ann Hygiene 36, 5, 1871;h 医学。Wochenschrift 28(第2名),21,1902)。甘氨酸抑制脂肪分解(另一种抗兴奋,“抗雌激素”的作用),这本身就会使胰岛素更有效,并有助于预防高血糖。(富含明胶的饮食也可以降低血清甘油三酯。)由于持续的脂解和胰岛素抵抗,以及广泛的炎症状态,涉及到许多疾病,特别是退行性疾病,所以考虑使用甘氨酸/明胶来治疗几乎所有的慢性疾病是合理的。(鸡爪汤在一些文化中被用于治疗各种疾病;鸡爪粉一直被提倡作为脊髓再生的兴奋剂——哈里·罗伯逊的方法被美国食品和药物管理局叫停了)。

Although Hans Selye observed as early as the 1930s that stress causes internal bleeding (in lungs, adrenals, thymus, intestine, salivary and tear glands, etc.), the medical establishment, which has the opportunity to see it after surgery, burns or other trauma, and following strokes and head injuries, prefers to explain it by “stomach hyperacidity,” as if it were limited to the stomach and duodenum. And the spontaneous bruising, and easy bruising, that is experienced by millions of women, especially with the premenstrual syndrome, and nose bleeds, and scleral bleeding, purpura senilis, urinary bleeding, bleeding gums, and many other kinds of “spontaneous” or stress related bleeding, are treated by main-line medicine as if they had no particular physiological significance.

Stress is an energy problem, that leads to the series of hormonal and metabolic reactions that I have often written about–lipolysis, glycolysis, increased serotonin, cortisol, estrogen, prolactin, leaky capillaries, protein catabolism, etc. The capillaries are among the first tissues to be damaged by stress.

Although Selye showed that estrogen treatment mimics shock and stress, and that progesterone prevents the stress reaction, the effects of these hormones on the circulatory system have never been treated systematically. Katherina Dalton observed that progesterone treatment prevented the spontaneous bruising of the premenstrual syndrome; Soderwall observed that estrogen caused enlargement of the adrenals, sometimes with hemorrhage and necrosis; old female animals often have bleeding in the adrenals (Dhom, et al., 1981). Strangely, estrogen's induction of uterine bleeding has been compartmentalized, as if the endometrial blood vessels didn't follow the same rules as vessels elsewhere in the body. Both estrogen and cortisol are known to cause clotting disorders and to increase capillary fragility, but these steroids have been elevated to the realm of billion dollar drug products, beyond the reach of ordinary physiological thinking. Other stress-released substances that are entangled in the drug market (tryptophan, serotonin, nitric oxide, and unsaturated fats, for example) are similarly exempt from consideration as factors in circulatory, neoplastic, and degenerative diseases.

尽管Hans Selye早在20世纪30年代就观察到压力会导致内出血(在肺、肾上腺、胸腺、肠、唾液腺和泪腺等),但在手术、烧伤或其他创伤后,以及中风和头部受伤后,医疗机构有机会看到内出血,更喜欢用“胃酸过多”来解释,好像它仅限于胃和十二指肠。自发瘀伤,以及容易瘀伤,这是数百万女性都经历过的,特别是经前综合症,鼻子出血,巩膜出血,老年紫癜,尿出血,牙龈出血,以及许多其他类型的“自发”或应激相关出血,被主流药物治疗,就好像它们没有特别的生理意义。

压力是一种能量问题,它会导致我经常写的一系列激素和代谢反应——脂解、糖酵解、血清素增加、皮质醇、雌激素、催乳素、毛细血管渗漏、蛋白质分解等等。毛细血管是压力最先破坏的组织之一。

尽管Selye研究表明雌激素治疗模拟休克和应激,而孕酮预防应激反应,但这些激素对循环系统的影响尚未得到系统治疗。Katherina Dalton观察到孕激素治疗可以防止经前综合症的自发性瘀伤;Soderwall观察到雌激素引起肾上腺增大,有时伴有出血和坏死;年老的雌性动物经常有肾上腺出血(Dhom, et al., 1981)。奇怪的是,雌激素诱导子宫出血的作用被分隔开了,就好像子宫内膜的血管并不像身体其他部位的血管一样遵循同样的规则。众所周知,雌激素和皮质醇都会导致凝血障碍和毛细血管脆性增加,但这些类固醇已经被提升到价值数十亿美元的药品领域,超出了普通生理思维的范围。在药物市场中,其他释放压力的物质(例如色氨酸、血清素、一氧化氮和不饱和脂肪)同样被排除在循环、肿瘤和退行性疾病的因素之外。

At the time Selye was observing stress-induced bleeding, standard medicine was putting gelatin to use–orally, subcutaneously, and intravenously–to control bleeding. Since ancient times, it had been used to stop bleeding by applying it to wounds, and this had finally been incorporated into medical practice.

The 1936 Cyclopedia of Medicine (G.M. Piersol, editor, volume 6) mentions the use of gelatin solution to quickly control nosebleeds, excessive menstrual bleeding, bleeding ulcers (using three doses of 18 grams as a 10% solution during one day), and bleeding from hemorrhoids and the lower bowel, and hemorrhage from the bladder. But since Selye's work relating the thrombohemorrhagic syndromes to stress wasn't known at that time, gelatin was thought of as a useful drug, rather than as having potentially far-reaching physiological effects, antagonizing some of the agents of stress-induced tissue damage.

Skin cells and nerve cells and many other cells are “electrically” stabilized by glycine, and this effect is currently being described in terms of a “chloride current.” A variety of mechanisms have been proposed for the protective effects of some of the amino acids, based on their use as energy or for other metabolic purpose, but there is evidence that glycine and alanine act protectively without being metabolized, simply by their physical properties.

在Selye观察压力引起的出血时,标准的药物是使用明胶——口服、皮下和静脉注射——来控制出血。自古以来,人们就用它来止血,把它敷在伤口上,这最终被纳入医疗实践。

1936年医学百科全书(通用Piersol、编辑、卷6)提到的使用明胶溶液快速控制流鼻血,过度的月经出血,出血溃疡(使用三个剂量的18克10%的解决方案在一天),痔疮出血和肠道越低,从膀胱出血。但由于Selye将血栓出血性综合症与压力联系起来的研究在当时还不为人所知,明胶被认为是一种有用的药物,而不是具有潜在的深远的生理效应,可以对抗压力引起的组织损伤的一些因素。

皮肤细胞、神经细胞和许多其他细胞被甘氨酸“电”稳定下来,这种效应目前被描述为“氯化物电流”。基于某些氨基酸作为能量或用于其他代谢目的,已经提出了各种各样的保护作用机制,但有证据表明,甘氨酸和丙氨酸在不被代谢的情况下起保护作用,仅仅是通过它们的物理特性。

A small dose of glycine taken shortly after suffering a stroke was found to accelerate recovery, preventing the spreading of injury through its inhibitory and antiinflammatory actions. Its nerve-stabilizing action, increasing the amount of stimulation required to activate nerves, is protective in epilepsy, too. This effect is important in the regulation of sleep, breathing, and heart rhythm.

Glycine's antispastic activity has been used to alleviate the muscle spasms of multiple sclerosis. It is thought to moderate some of the symptoms of schizophrenia.

A recent publication shows that glycine alleviates colitis; but the use of gelatin, especially in the form of a concentrated gelatinous beef broth, for colitis, dysentery, ulcers, celiac disease, and other diseases of the digestive system, goes far back in medical history. Pavlov's observation of its effectiveness in stimulating the secretion of digestive juices occurred because the stimulating value of broth was already recognized.

在中风后不久服用小剂量的甘氨酸被发现可以加速恢复,通过其抑制和抗炎作用防止损伤的扩散。它的神经稳定作用,增加了激活神经所需的刺激量,对癫痫也有保护作用。这种效果在调节睡眠、呼吸和心率方面很重要。

甘氨酸的抗痉挛作用已被用于缓解多发性硬化症的肌肉痉挛。它被认为可以缓解精神分裂症的一些症状。

最近发表的一篇文章表明,甘氨酸可以缓解结肠炎;但是明胶的使用,尤其是以浓缩的明胶牛肉汤的形式,用于治疗结肠炎、痢疾、溃疡、腹腔疾病和其他消化系统疾病,在医学史上可以追溯到很久以前。巴甫洛夫观察到它在刺激消化液分泌方面的有效性是因为肉汤的刺激价值已经被认识到。

Although I pointed out a long time ago the antithyroid effects of excessive cysteine and tryptophan from eating only the muscle meats, and have been recommending gelatinous broth at bedtime to stop nocturnal stress, it took me many years to begin to experiment with large amounts of gelatin in my diet. Focusing on the various toxic effects of tryptophan and cysteine, I decided that using commercial gelatin, instead of broth, would be helpful for the experiment. For years I hadn't slept through a whole night without waking, and I was in the habit of having some juice or a little thyroid to help me go back to sleep. The first time I had several grams of gelatin just before bedtime, I slept without interruption for about 9 hours. I mentioned this effect to some friends, and later they told me that friends and relatives of theirs had recovered from long-standing pain problems (arthritic and rheumatic and possibly neurological) in just a few days after taking 10 or 15 grams of gelatin each day.

For a long time, gelatin's therapeutic effect in arthritis was assumed to result from its use in repairing the cartilage or other connective tissues around joints, simply because those tissues contain so much collagen. (Marketers suggest that eating cartilage or gelatin will build cartilage or other collagenous tissue.) Some of the consumed gelatin does get incorporated into the joint cartilage, but that is a slow process, and the relief of pain and inflammation is likely to be almost immediate, resembling the antiinflammatory effect of cortisol or aspirin.

Inflammation produces fibrosis, because stress, hypoxia, and inadequate supply of glucose stimulate the fibroblasts to produce increased amounts of collagen. In lungs, kidneys, liver, and other tissues, glycine protects against fibrosis, the opposite of what the traditional view would suggest.

虽然我很久以前就指出过度的半胱氨酸和色氨酸的抗甲腺的影响从肌肉肉,只吃,建议睡前凝胶状的肉汤停止夜间压力,我花了许多年才开始尝试大量的明胶在我的饮食。专注于色氨酸和半胱氨酸的各种毒性作用,我决定使用商业明胶,而不是肉汤,将有助于实验。多年来,我没有一整夜不醒地睡过觉,我习惯喝点果汁或吃点甲状腺药来帮助我重新入睡。第一次我在睡前吃了几克明胶,我连续睡了大约9个小时。我向一些朋友提到了这种效果,后来他们告诉我,他们的朋友和亲戚在每天服用10到15克明胶后,在几天内就从长期的疼痛问题(关节炎、风湿性疾病,可能还有神经系统疾病)中恢复了过来。

长期以来,明胶对关节炎的治疗效果被认为是由于它用于修复软骨或关节周围的其他结缔组织,仅仅因为这些组织含有大量的胶原蛋白。(营销人员建议,吃软骨或明胶可以构建软骨或其他胶原组织。)食用的一些明胶确实会进入关节软骨,但这是一个缓慢的过程,疼痛和炎症的缓解可能几乎是立即的,类似于皮质醇或阿司匹林的抗炎作用。

炎症导致纤维化,因为压力、缺氧和葡萄糖供应不足刺激成纤维细胞产生更多的胶原蛋白。在肺、肾、肝和其他组织中,甘氨酸可以防止纤维化,这与传统观点所认为的相反。

Since excess tryptophan is known to produce muscle pain, myositis, even muscular dystrophy, gelatin is an appropriate food for helping to correct those problems, simply because of its lack of tryptophan. (Again, the popular nutritional idea of amino acids as simply building blocks for tissues is exactly wrong–muscle protein can exacerbate muscle disease.) All of the conditions involving excess prolactin, serotonin, and cortisol (autism, postpartum and premenstrual problems, Cushing's disease, “diabetes,” impotence, etc.) should benefit from reduced consumption of tryptophan. But the specifically antiinflammatory amino acids in gelatin also antagonize the excitatory effects of the tryptophan-serotonin-estrogen- prolactin system.

In some of the older studies, therapeutic results improved when the daily gelatin was increased. Since 30 grams of glycine was commonly used for treating muscular dystrophy and myasthenia gravis, a daily intake of 100 grams of gelatin wouldn't seem unreasonable, and some people find that quantities in that range help to decrease fatigue. For a growing child, though, such a large amount of refined gelatin would tend to displace other important foods. The National Academy of Sciences recently reviewed the requirements for working adults (male and female soldiers, in particular), and suggested that 100 grams of balanced protein was needed for efficient work. For adults, a large part of that could be in the form of gelatin.

If a person eats a large serving of meat, it's probably helpful to have 5 or 10 grams of gelatin at approximately the same time, so that the amino acids enter the blood stream in balance.

Asian grocery stores are likely to sell some of the traditional gelatin-rich foods, such as prepared pig skin and ears and tails, and chicken feet.

众所周知,过量的色氨酸会产生肌肉疼痛、肌炎,甚至肌肉营养不良,仅仅因为缺乏色氨酸,明胶就是一种帮助纠正这些问题的合适食物。(同样,流行的营养学观点认为氨基酸只是构成组织的基础,这是完全错误的——肌肉蛋白质会加剧肌肉疾病。)所有涉及催乳素、血清素和皮质醇过量的疾病(自闭症、产后和经前问题、库欣病、“糖尿病”、阳痿等)都应该从减少色氨酸的摄入中受益。但是明胶中特殊的抗炎氨基酸也能拮抗色氨酸-血清素-雌激素-催乳素系统的兴奋作用。

在一些较早的研究中,当每天增加明胶时,治疗效果有所改善。由于30克甘氨酸通常用于治疗肌肉萎缩症和重症肌无力,每天摄入100克明胶似乎没有什么不合理的,一些人发现这个范围内的量有助于减少疲劳。然而,对于一个正在成长的孩子来说,如此大量的精制明胶可能会取代其他重要的食物。美国国家科学院(National Academy of Sciences)最近审查了工作成年人(尤其是男性和女性士兵)的需求,并建议100克均衡蛋白质是高效工作所必需的。对于成年人来说,其中很大一部分可能以明胶的形式存在。

如果一个人吃了一大块肉,大约同时摄入5到10克明胶可能是有帮助的,这样氨基酸就能平衡地进入血液。

亚洲的杂货店可能会出售一些传统的富含明胶的食物,比如预制猪皮、猪耳朵和猪尾巴,以及鸡爪。

Although the prepared powdered gelatin doesn't require any cooking, dissolving it in hot water makes it digest a little more quickly. It can be incorporated into custards, mousses, ice cream, soups, sauces, cheese cake, pies, etc., or mixed with fruit juices to make desserts or (with juice concentrate) candies.

Although pure glycine has its place as a useful and remarkably safe drug, it shouldn't be thought of as a food, because manufactured products are always likely to contain peculiar contaminants.

虽然准备好的粉状明胶不需要任何烹饪,但将它溶解在热水中会让它消化得更快一些。它可以与奶油冻、慕斯、冰淇淋、汤、酱汁、奶酪蛋糕、派等混合,也可以与果汁混合制成甜点或(浓缩果汁)糖果。

尽管纯甘氨酸是一种有用且非常安全的药物,但它不应该被认为是一种食品,因为生产出来的产品总是可能含有特殊的污染物。

REFERENCES 

Am J Physiol. 1990 Jul;259(1 Pt 2):F80-7. Mechanisms of perfused kidney cytoprotection by alanine and glycine. Baines AD, Shaikh N, Ho P.

Neurol. 1974; 24:392. Preliminary study of glycine administration in patients with spasticity. Barbeau A.

Virchows Arch B Cell Pathol Incl Mol Pathol. 1981;36(2-3):195-206. Peliosis of the female adrenal cortex of the aging rat. Dhom G, Hohbach C, Mausle E, Scherr O, Uebergerg H. Foci of apparent peliosis are regularly observed in the mid-zone of the adrenal cortex in female rats older than 600 days. The changes present range from ectasis of the sinusoids to extensive cystic change of the whole organ. This lesion occurs almost exclusively in female animals and was seen in only one of 50 male animals older than 600 days examined. Experimental stimulation or inhibition did not influence adrenal peliosis. Electron microscopically, there was marked pericapillary edema with collapse of the capillaries, and erythrocytes and thrombocytes were seen infiltrating the edema. Fibrin accumulated in the larger foci. Degenerative alterations were not observed either in the epithelial cells of the cortex or in mesenchymal cells. The pathogenesis is unknown, but the possible role of constant estrus in aging female rats will be discussed.

Riv Neurol. 1976 Mar-Jun;46(3):254-61. [Antagonism between focal epilepsy and taurine administered by cortical Perfusion] Durelli L, Quattrocolo G, Buffa C, Valentini C, Mutani R. The therapeutic action of taurine cortical perfusion was tested in cats affected with Premarin and cobalt cortical epileptogenic foci. In all animals taurine provoked the disappearance of EEG epileptic abnormalities. In the case of Premarin focus the effect appeared more quickly than in the cobalt one. This different time-course, according to previous reports on the antiepileptic action of the parenteral administration of the amino acid, suggests the hypothesis of a taurine direct inhibitory action against Premarin focus and, on the contrary, a mediated action towards the cobalt's. The latter might be related to the metabolic production of some taurine derivative.

Ann Neurol. 1998; 44:261-265. Beneficial effects of L-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency. de Kooning JT, Duran M, Dorling L, et al.

Arch Gen Psychiatry. 1999; 56:29-36. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Heresco-Levy U, Javitt DC, Ermilov M, et al.

Free Radic Biol Med. 2001 Nov 15;31(10):1236-44. Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat. Mauriz JL, Matilla B, Culebras JM, Gonzalez P, Gonzalez-Gallego J. “Feeding the rats glycine significantly reduced mortality, the elevation of plasma transaminase levels and hepatic necrosis. The increase in plasma TNFalpha and nitric oxide (NO) was also blunted by glycine feeding.”

Am Fam Phys 1979 May;19(5):77-86. 'Not Cushing's syndrome'. Rincon J, Greenblatt RB, Schwartz RP Cushing's syndrome is characterized by protein wasting secondary to hypergluconeogenesis, which produces thin skin, poor muscle tone, osteoporosis and capillary fragility. These features distinguish patients with true Cushing's syndrome from those who have some of the clinical findings often associated with the syndrome, such as obesity, hypertension, striae and hirsutism. The dexamethasone suppression test helps identify patients with pseudo-Cushing's syndrome.

Carcinogenesis. 1999; 20:2075-2081. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14, 643. Rose ML, Cattley RC, Dunn C, et al.

Carcinogenesis, Vol. 20, No. 5, 793-798, May 1999. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Rose M.L.,Madren J, Bunzendahl H., and Thurman R.G. Dietary glycine inhibited hepatocyte proliferation in response to the carcinogen WY-14,643. Since increased cell replication is associated with hepatic cancer caused by WY-14,643, glycine may have anti-cancer properties. Therefore, these experiments were designed to test the hypothesis that dietary glycine would inhibit the growth of tumors arising from B16 melanoma cells implanted subcutaneously in mice. C57BL/6 mice were fed diet supplemented with 5% glycine and 15% casein or control diet (20% casein) for 3 days prior to subcutaneous implantation of B16 tumor cells. Weight gain did not differ between mice fed control and glycine-containing diets. B16 tumors grew rapidly in mice fed control diet; however, in mice fed glycine diet, tumor size was 50-75% less. At the time of death, tumors from glycine-fed mice weighed nearly 65% less than tumors from mice fed control diet (P < 0.05). Glycine (0.01-10 mM) did not effect growth rates of B16 cells in vitro. Moreover, tumor volume and mitotic index of B16 tumors in vivo did not differ 2 days after implantation when tumors were small enough to be independent of vascularization. After 14 days, tumors from mice fed dietary glycine had 70% fewer arteries (P < 0.05). Furthermore, glycine (0.01-10 mM) inhibited the growth of endothelial cells in vitro in a dose-dependent manner (P < 0.05; IC50 = 0.05 mM). These data support the hypothesis that dietary glycine prevents tumor growth in vivo by inhibiting angiogenesis through mechanisms involving inhibition of endothelial cell proliferation.

Carcinogenesis, Vol. 20, No. 11, 2075-2081, November 1999. Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643. M.L.Rose, R.C.Cattley1, C.Dunn, V.Wong, Xiang Li and R.G.Thurman. Simpson RK Jr, Gondo M, Robertson CS, Goodman JC. The influence of glycine and related compounds on spinal cord injury-related spasticity. Neurochem Res. 1995; 20:1203-1210.

Neurochem Res. 1995 Oct;20(10):1203-10. The influence of glycine and related compounds on spinal cord injury-induced spasticity. Simpson RK Jr, Gondo M, Robertson CS, Goodman JC.

Neurochem Res. 1996 Oct;21(10):1221-6. Reduction in the mechanonociceptive response by intrathecal administration of glycine and related compounds. Simpson RK Jr, Gondo M, Robertson CS, Goodman JC.

Neurol Res. 1998 Mar;20(2):161-8. Glycine receptor reduction within segmental gray matter in a rat model in neuropathic pain. Simpson RK Jr, Huang W.

Neurol Res. 2000 Mar;22(2):160-4. Long-term intrathecal administration of glycine prevents mechanical hyperalgesia in a rat model of neuropathic pain. Huang W, Simpson RK.

Pharmacol Biochem Behav. 1992 Nov;43(3):669-71. Branched-chain amino acids increase the seizure threshold to picrotoxin in rats. Skeie B, Petersen AJ, Manner T, Askanazi J, Jellum E, Steen PA.

Thromb Diath Haemorrh Suppl 1968;30:165-9 [Purpura of the premenstrum and climacteric]. [Article in German] Stamm H.

Toth E, Lajtha A. Glycine potentiates the action of some anticonvulsant drugs in some seizure models. Neurochem Res. 1984; 9:1711-1718.

Sheng Li Ke Xue Jin Zhan. 2000 Jul;31(3):231-3. [The roles of estrogen and progestin in epileptogenesis and their mechanisms of action] [Article in Chinese] Wang Q.

FASEB J. 2000; 14:476-484. Glycine-gated channels in neutrophils attenuate calcium influx and superoxide production. Wheeler M, Stachlewitz RT, Yamashina S, et al.

Cell Mol Life Sci.1999; 56:843-856. Glycine: a new anti-inflammatory immunonutrient. Wheeler MD, Ikejema K, Mol Life Sci. Enomoto N, et al.

Nutr Cancer. 2001;40(2):197-204. Endothelial cells contain a glycine-gated chloride channel. Yamashina S, Konno A, Wheeler MD, Rusyn I, Rusyn EV, Cox AD, Thurman RG. “Glycine inhibited growth of B16 melanoma tumors in vivo most likely because of the inhibition of angiogenesis. Here, the hypothesis that the anticancer effect of glycine in vivo is due to expression of a glycine-gated Cl- channel in endothelial cells was tested.

Biull Eksp Biol Med. 1981 Nov;92(11):599-601. [Repair processes in wound tissues of experimental animals following administration of glycine] [Article in Russian] Zaidenberg MA, Pisarzhevskii SA, Nosova IM, Kerova AN, Dudnikova GN. A study was made of the effect of glycine given in doses approximating the physiological ones on the repair of processes in rat wound tissues. It was disclosed that in the early periods of wound healing, glycine administration leads to the increased content of cAMP and cAMP/cGMP ratio in the wound muscle and then in the granulation tissue, which appears to promote the intensification of the repair processes manifesting in the changes in tissue metabolism (DNA, collagen), in anti-inflammatory action, as well as in a more rapid maturation of the granulation tissue and wound reduction.. It was also found that the doses of glycine tested do not affect the content of insulin and hydrocortisone in the blood of experimental animals. 

“In recent years, evidence has mounted in favor of the antiinflammatory, immunomodulatory and cytoprotective effects of the simplest amino acid L-glycine.” “Glycine protects against shock caused by hemorrhage, endotoxin and sepsis, prevents ischemia/reperfusion and cold storage/reperfusion injury to a variety of tissues and organs including liver, kidney, heart, intestine and skeletal muscle, and diminishes liver and renal injury caused by hepatic and renal toxicants and drugs. Glycine also protects against peptidoglycan polysaccharide-induced arthritis…” and inhibits gastric secretion “….and protects the gastric mucosa against chemically and stress-induced ulcers. Glycine appears to exert several protective effects, including antiinflammatory, immunomodulatory and direct cytoprotective actions. Glycine acts on inflammatory cells such as macrophages to suppress activation of transcription factors and the formation of free radicals and inflammatory cytokines. In the plasma membrane, glycine appears to activate a chloride channel that stabilizes or hyperpolarizes the plasma membrane potential. As a consequence, …. opening of … calcium channels and the resulting increases in intracellular calcium ions are suppressed, which may account for the immunomodulatory and antiinflammatory effects of glycine. Lastly, glycine blocks the opening of relatively non-specific pores in the plasma membrane that occurs as the penultimate event leading to necrotic cell death.”

Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P, Yin M, Bunzendaul H, Bradford B, Lemasters JJ., “L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent.” Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):229-40.

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