Estrogen and Osteoporosis
雌激素和骨质疏松症
by Raymond Peat
“How does estrogen enhance endotoxin toxicity? Let me count the ways.”
J.J. Maher (Liver Center and Department of Medicine, University of California San Francisco) in Hepatology, 1998, 28(6):1720-1.
“雌激素是如何增强内毒素毒性的?”让我细数一下。”
The government declared victory in the war on cancer, though the age-specific death rate from cancer keeps increasing. In the equally well publicized effort to prevent disability and death from osteoporosis, no one is declaring victory, because the only trend in its incidence that has been reported is an increase. The estrogen-promoting culture tells us that this is because of the aging of the population, but the age corrected numbers still show a great increase–for example, in Finland between 1970 and 1995, the number of women (for a given population of women older than 60) breaking their forearm because of osteoporosis more than doubled (Palvanen, et al., 1998). That this happened during a time when the use of estrogen had become much more common doesn't present a good argument for the protective effects of estrogen treatment. (And during this period there was a large increase in the consumption of estrogenic soy products.) Recently our local newspaper had a story at the bottom of the front page reporting that lean women who used estrogen and synthetic progestins had an 80% higher rate of breast cancer. Several days later, across the top of the front page, there was a rebuttal article, quoting some doctors including a “world class expert on hormone replacement therapy” and a woman who has taken Premarin for forty years and urges everyone to take it. The “protection against osteoporosis” and against heart disease, they said, must be weighed against a trifle such as the 80% increase in cancer. It appeared that the newspaper was apologizing for reporting a fact that could make millions of women nervous. (Jan 26, Register-Guard).
政府宣布在与癌症的战争中取得了胜利，尽管按年龄划分的癌症死亡率不断上升。在同样广为宣传的预防骨质疏松症导致残疾和死亡的努力中，没有人宣称取得了胜利，因为据报道，骨质疏松症发病率的唯一趋势是增加。estrogen-promoting文化告诉我们,这是因为人口老龄化的,但年龄校正数据仍然显示一个伟大的增加——例如,在芬兰在1970年至1995年之间,女性的数量(对于一个给定的人口年龄超过60岁的女性)骨质疏松症的打破他们的前臂,因为增加了一倍多(Palvanen,et al ., 1998)。这种情况发生在使用雌激素变得更加普遍的时期，这并不能很好地证明雌激素治疗的保护作用。(在此期间，雌激素类豆制品的消费量大幅增加。)最近，我们当地的报纸在头版底部刊登了一则报道，报道说使用雌激素和合成黄体酮的瘦弱女性患乳腺癌的几率高出80%。几天后，在头版的顶部，有一篇反驳文章，引用了一些医生的话，包括一位“荷尔蒙替代疗法的世界级专家”和一位服用普雷玛林40年的妇女，她敦促所有人都服用普雷玛林。他们说，“对骨质疏松症的保护”和对心脏病的保护，必须与诸如癌症增加80%这样的小事相权衡。该报似乎在为报道一件可能让数百万女性感到紧张的事实而道歉。(1月26日,Register-Guard)。
Medical magazines, like the mass media, don't like to miss any opportunity to inform the public about the importance of using estrogen to prevent osteoporosis. Their attention to the bone-protective effect of progesterone has been noticeably less than their mad campaign to sell estrogen, despite the evidence that progesterone can promote bone rebuilding, rather than just slowing its loss. Although I have spoken about progesterone and osteoporosis frequently in the last 25 years, I have only occasionally considered what estrogen does to bones; generally, I described estrogen as a stress-promoting and age-promoting hormone. In the 1970s, pointing out progesterone's protective antagonism to excessive amounts of other hormones, and that the catabolic glucocorticoids tend to increase with aging, I began referring to progesterone as the “anticatabolic” hormone that should be used to prevent stress-induced atrophy of skin, bones, brain, etc.
医学杂志，像大众媒体一样，不愿意错过任何机会，告诉公众使用雌激素预防骨质疏松症的重要性。尽管有证据表明，黄体酮可以促进骨骼重建，而不仅仅是减缓骨骼损失，但他们对黄体酮保护骨骼作用的关注明显不如他们疯狂地推销雌激素。虽然在过去的25年里，我经常谈论黄体酮和骨质疏松症，但我只是偶尔考虑一下雌激素对骨骼的影响;总的来说，我把雌激素描述为一种促进压力和年龄增长的激素。在1970年代,指出孕酮的保护对抗其他激素过量,并且与老化分解糖皮质激素增加,我开始指孕酮作为“抗分解代谢”应该用于防止应激激素的皮肤萎缩,骨骼、大脑等。
A former editor of Yearbook of Endocrinology had reviewed a series of studies showing that excess prolactin can cause osteoporosis. Then, he presented a group of studies showing how estrogen promotes the secretion of prolactin, and can cause hyperprolactinemia. In that review, he wryly wondered how something that increases something that causes osteoporosis could prevent osteoporosis.
《内分泌学年鉴》(Yearbook of Endocrinology)的前编辑回顾了一系列研究，表明过量的催乳素会导致骨质疏松。然后，他提出了一组研究，表明雌激素如何促进催乳素的分泌，并可能导致高催乳素血症。在那篇综述中，他苦笑地想知道，增加导致骨质疏松的物质的东西是如何预防骨质疏松的。
Women have a higher incidence of osteoporosis than men do. Young women have thinner more delicate bones than young men. The women who break bones in old age are generally the women who had the thinnest bones in youth. Menstrual irregularities, and luteal defects, that involve relatively high estrogen and low progesterone, increase bone loss.
女性患骨质疏松症的几率高于男性。年轻女性的骨头比年轻男性的骨头更细。在老年骨折的女性通常是年轻时骨骼最薄的女性。月经不规律和黄体缺陷，包括相对较高的雌激素和较低的黄体酮，会增加骨质流失。
Fatter women are less likely to break bones than thinner women. Insulin, which causes the formation of fat, also stimulates bone growth. Estrogen however, increases the level of free fatty acids in the blood, indicating that it antagonizes insulin (insulin decreases the level of free fatty acids), and the fatty acids themselves strongly oppose the effects of insulin. Estrogen dominance is widely thought to predispose women to diabetes.
胖女人比瘦女人更不容易骨折。导致脂肪形成的胰岛素，也会刺激骨骼生长。而雌激素则会增加血液中游离脂肪酸的含量，这表明雌激素能拮抗胰岛素(胰岛素降低游离脂肪酸的含量)，而脂肪酸本身又强烈地反对胰岛素的作用。雌激素过多被广泛认为使妇女易患糖尿病。
Between the ages of 20 and 40, there is a very considerable increase in the blood level of estrogen in women. However, bone loss begins around the age of 23, and progesses through the years when estrogen levels are rising. Osteoarthritis, which involves degeneration of the bones around joints, is strongly associated with high levels of estrogen, and can be produced in animals with estrogen treatment.
在20到40岁之间，女性血液中的雌激素水平有相当大的增加。然而，骨质流失开始于23岁左右，并随着雌激素水平的上升而持续。骨关节炎涉及关节周围骨骼的退化，与高水平的雌激素密切相关，在使用雌激素治疗的动物身上可以产生骨关节炎。
Thirty years ago, when people were already claiming that estrogen would prevent or cure osteoporosis, endocrinologists pointed out that there was no x-ray evidence to support the claim. Estrogen can cause a positive calcium balance, the retention of more calcium than is excreted, and the estrogen promoters argued that this showed it was being stored in the bones, but the endocrine physiologists showed that estrogen causes the retention of calcium by soft tissues. There are many reasons for not wanting calcium to accumulate in the soft tissues; this occurs normally in aging and stress.
30年前，当人们声称雌激素可以预防或治愈骨质疏松症时，内分泌学家指出，并没有x射线证据支持这一说法。雌激素能促进钙的平衡，保留的钙多于排出的钙，雌激素促进者认为这表明钙被储存在骨骼中，但内分泌生理学家表明雌激素导致钙被软组织保留。有很多原因不希望钙在软组织中积累;这通常发生在衰老和压力中。
Then, it was discovered that, although estrogen doesn't improve the activity of the cells that build bone, it can reduce the activity of the cells that remove bone, the osteoclasts. The osteoclast is a type of phagocytic cell, and is considered to be a macrophage, the type of cell that can be found in any organ, which can eat any sort of particle, and which secretes substances (cytokines, hormone-like proteins) that modify the functions of other cells. When estrogen was found to impair the activity of this kind of cell, there wasn't much known about macrophage cytokines.
然后，研究人员发现，尽管雌激素不能提高造骨细胞的活性，但它可以降低清除骨的细胞，即破骨细胞的活性。破骨细胞是一种吞噬细胞，被认为是一种巨噬细胞，这种细胞可以在任何器官中找到，可以吃任何种类的颗粒，并分泌改变其他细胞功能的物质(细胞因子，激素样蛋白质)。当雌激素被发现损害这类细胞的活性时，对巨噬细胞因子的了解并不多。
With the clear evidence that estrogen inhibits the osteoclasts without activating the bone-building osteoblasts, estrogen was said to “prevent bone loss,” and from that point on we never heard again about estrogen promoting a positive calcium balance. Calcium retention by soft tissues has come to be an accepted marker of tissue aging, tissue damage, excitotoxicity, and degeneration. Positive calcium balance had been the essence of the argument for using estrogen to prevent osteoporosis: “Women are like chickens, estrogen makes them store calcium in their bones.” But if everyone now recognizes that calcium isn't being stored in bones, it's better for the estrogen industry if we forget about the clearly established positive calcium balance produced by estrogen.
有明确的证据表明，雌激素抑制破骨细胞而不激活造骨细胞，雌激素被称为“防止骨质流失”，从那以后，我们再也没有听说过雌激素促进钙平衡。软组织钙潴留已成为公认的组织老化、组织损伤、兴奋性毒性和变性的标志。正钙平衡一直是使用雌激素预防骨质疏松的争论的核心:“女性就像鸡一样，雌激素使她们在骨骼中储存钙。”但是，如果现在每个人都认识到钙不是储存在骨骼中，如果我们忘记雌激素产生的明确的正钙平衡，这对雌激素产业是更好的。
The toxic effects of excessive intracellular calcium (decreased respiration and increased excitation) are opposed by magnesium. Both thyroid and progesterone improve magnesium retention. Estrogen dominance is often associated with magnesium deficiency, which can be an important factor in osteoporosis (Abraham and Grewal, 1990; Muneyyirci-Delale, et al., 1999). As part of the campaign to get women to use estrogen, an x-ray (bone density) test was devised which can supposedly measure changes in the mineral content of bone. However, it happens that fat and water interfere with the measurements. Estrogen changes the fat and water content of tissues. By chance, the distortions produced by fat and water happen to be such that estrogen could appear to be increasing the density of a bone, when it is really just altering the soft tissues. Ultrasound measurements can provide very accurate measurements of bone density, without the fat and water artifacts that can produce misleading results in the x-ray procedure, and don't expose the patient to radiation, but the ultrasound method is seldom used.
细胞内钙过量的毒性作用(呼吸减少和兴奋增加)与镁相反。甲状腺和黄体酮都能改善镁潴留。雌激素占优势通常与镁缺乏有关，这可能是骨质疏松症的一个重要因素(Abraham和Grewal, 1990;muneyirci - delale等，1999)。作为让女性使用雌激素运动的一部分，x射线(骨密度)测试被设计出来，据称可以测量骨骼中矿物质含量的变化。然而，脂肪和水会干扰测量结果。雌激素改变组织的脂肪和水分含量。巧合的是，脂肪和水产生的扭曲恰好是这样的，雌激素可能会增加骨骼的密度，而实际上它只是改变了软组织。超声测量可以提供非常精确的骨密度测量，没有脂肪和水伪影，这些伪影会在x光检查过程中产生误导的结果，而且不会让病人暴露在辐射中，但超声方法很少被使用。
In recent years, there has been quite a lot of research into the effects of the macrophage cytokines. Immune therapy for cancer was considered quackery when Lawrence Burton identified some substances in blood serum that could cause massive tumors in rodents to disappear in just a few hours. One of the serum factors was called Tumor Necrosis Factor, TNF. An official committee was formed to evaluate his work, but it reported that there was nothing to it. A member of the committee later became known as “the authority” on tumor necrosis factor, which was thought to have great potential as an anticancer drug. However, used by itself, TNF killed only a few cancers, but it damaged every organ of the body, usually causing the tissues to waste away. Other names, lymphotoxin and cachectin, reflected its toxic actions on healthy tissues.
近年来，人们对巨噬细胞因子的作用进行了大量的研究。当劳伦斯·伯顿在血清中发现某些物质可以导致啮齿动物体内的巨大肿瘤在几小时内消失时，癌症的免疫疗法被认为是江湖骗术。其中一个血清因子称为肿瘤坏死因子(TNF)。成立了一个正式的委员会来评价他的工作，但委员会报告说没什么可做的。该委员会的一名成员后来被称为肿瘤坏死因子的“权威”，被认为是一种具有巨大潜力的抗癌药物。然而，单独使用TNF只杀死了少数癌症，但它损害了身体的每个器官，通常导致组织损耗。其他名字，如淋巴毒素和cachectin，反映了它对健康组织的毒性作用。
Aging involves many changes that tend to increase the inflammatory reaction, and generally the level of TNF increases with aging. Although cancer, heart failure, AIDS, and extreme hormone deficiency (from loss of the pituitary or thyroid gland, for example) can cause cachexia of an extreme and rapid sort, ordinary aging is itself a type of cachexia. Progeria, or premature aging, is a kind of wasting disease that causes a child's tissues (including bones) to atrophy, and to change in many of the ways that would normally occur in extreme old age.
衰老涉及许多倾向于增加炎症反应的变化，通常TNF的水平随衰老而增加。虽然癌症、心力衰竭、艾滋病和极度的激素缺乏(例如垂体或甲状腺的缺失)会导致极度快速的恶病质，但普通的衰老本身就是恶病质的一种。早衰症，或称过早衰老，是一种消耗性疾病，会导致儿童的组织(包括骨骼)萎缩，并在许多方面发生正常情况下在极度老年时才会发生的变化。
Recent studies have found that both men and women lose minerals from their bones at the rate of about 1% per year. Although men have lower estrogen in youth than women do, their bones are much heavier. During aging, as their bones get thinner, men's estrogen levels keep rising.
Besides having weaker bones, old people have weaker muscles, and are more likely to injure themselves in a fall because their muscles don't react as well. Muscle loss occurs at about the rate of 1% per year.
Women's muscles, like their bones, are normally smaller than men's, and estrogen contributes significantly to these differences.
最近的研究发现，男性和女性的骨骼中矿物质的流失速度约为每年1%。虽然年轻时男性的雌激素比女性低，但他们的骨骼要重得多。在衰老过程中，随着骨骼变薄，男性的雌激素水平不断上升。
除了骨骼较弱，老年人的肌肉也较弱，而且更容易在摔倒时受伤，因为他们的肌肉反应不佳。肌肉损失的发生率约为每年1%。
女性的肌肉，就像她们的骨骼一样，通常比男性的要小，而雌激素对这些差异起着重要的作用。
TNF can produce very rapid loss of tissue including bone, and in general, it rises with aging. Some of the people who like to say that “osteoporosis is caused by estrogen deficiency” know about the destructive actions of TNF, and argue that it rises at menopause “because of estrogen deficiency.” There are very good reasons for rejecting that argument; the experiments sometimes seem to have been designed purely for propaganda purposes, using toxic levels of estrogen for a specific result.
TNF能导致包括骨在内的组织迅速流失，一般来说，它会随着年龄的增长而增加。一些喜欢说“骨质疏松症是由雌激素缺乏引起的”的人知道TNF的破坏性作用，并认为它在更年期上升“因为雌激素缺乏”。我们有很好的理由来驳斥这一论点;这些实验有时似乎纯粹是为了宣传目的而设计的，使用有毒水平的雌激素来达到特定的结果。
One researcher noted that the effects of estrogen on cells in vitro are biphasic: Low doses increased TNF, high doses decreased TNF. Everyone knows that unphysiologically high doses (50 or 100 or more times above the physiological level of around 0.25 micrograms per liter) of estrogen are toxic to cells, producing functional and structural changes, and even rapid death. So, when a researcher who wants to show estrogen's “bone protective” effect of lowering TNF adds a lethal dose of estrogen to his cell culture, he can conclude that “estrogen inhibits TNF production.” But the result is no more interesting than the observation that a large dose of cyanide inhibits breathing.
一位研究人员指出，雌激素对体外细胞的影响是双向的:低剂量增加TNF，高剂量减少TNF。大家都知道，非生理水平的高剂量雌激素(比生理水平0.25微克/升高出50或100倍或更多)对细胞是有毒的，会产生功能和结构上的变化，甚至会导致快速死亡。因此，当一个研究人员想要展示雌激素降低TNF的“骨保护”作用时，他可以在细胞培养中加入致死剂量的雌激素，他可以得出“雌激素抑制TNF的产生”的结论。但其结果并不比大剂量氰化物抑制呼吸的观察更有趣。
TNF is produced by endotoxin, and estrogen increases the amount of endotoxin in the blood. Even without endotoxin, though, estrogen can stimulate the production of TNF. Lactic acid and unsaturated fats and hypoxia can stimulate increased formation of TNF. Estrogen increases production of nitric oxide systemically, and nitric oxide can stimulate TNF formation. How does TNF work, to produce tissue damage and wasting? It causes cells to take up too much calcium, which makes them hypermetabolic before it kills them. It increases formation of nitric oxide and carbon monoxide, blocking respiration. TNF can cause a 19.5 fold increased in the enzyme which produces carbon monoxide (Rizzardini, et al., 1993), which blocks respiration.
TNF由内毒素产生，雌激素增加血液中内毒素的数量。即使没有内毒素，雌激素也能刺激TNF的产生。乳酸、不饱和脂肪和缺氧可刺激TNF的形成增加。雌激素会增加全身一氧化氮的产生，而一氧化氮可以刺激TNF的形成。TNF如何工作，产生组织损伤和损耗?它会导致细胞吸收过多的钙，导致细胞在被杀死之前过度新陈代谢。它会增加一氧化氮和一氧化碳的形成，阻碍呼吸。TNF可导致产生一氧化碳的酶增加19.5倍(Rizzardini, et al.， 1993)，从而阻断呼吸。
All of the normal conditions associated with high estrogen also are found to involve increased production of TNF, and treatment of animals with estrogen clearly increases their TNF. Premature ovarian failure (with low estrogen levels) leads to reduced TNF, as does treatment with antiestrogens. If bone resorption is significantly regulated by TNF, then it should be concluded that increased estrogenic influence will tend to produce osteoporosis.
所有与高雌激素相关的正常情况也被发现与TNF的产生有关，用雌激素治疗动物明显增加了它们的TNF。卵巢早衰(雌激素水平低)导致TNF减少，抗雌激素治疗也是如此。如果骨吸收受到TNF的显著调节，那么可以得出结论，雌激素的影响会导致骨质疏松。
Tamoxifen, which has some estrogenic effects, including the inhibition of osteoclasts, can kill osteoclasts when the dose is high enough. The inhibition of osteoclast activity by either estrogen or tamoxifen is probably a toxic action, that has been characterized as “beneficial” by the estrogen industry simply because they didn't have any better argument for getting women to use their products.
三苯氧胺具有一定的雌激素作用，包括抑制破骨细胞，当剂量足够大时，可以杀死破骨细胞。雌激素或三苯氧胺对破骨细胞活性的抑制可能是一种毒性作用，而雌激素行业将其描述为“有益的”，只是因为他们没有更好的理由让女性使用他们的产品。
Some types of dementia, such as Alzheimer's disease, involve a life-long process of degeneration of the brain, with an inflammatory component, that probably makes them comparable to osteoporosis and muscle-wasting. (In the brain, the microglia, which are similar to macrophages, and the astrocytes, can produce TNF.) The importance of the inflammatory process in Alzheimer's disease was appreciated when it was noticed that people who used aspirin regularly had a low incidence of that dementia. Aspirin inhibits the formation of TNF, and aspirin has been found to retard bone loss. In the case of osteoporosis (A. Murrillo-Uribe, 1999), as in Alzheimer's disease, the incidence is two or three times as high in women as in men. In both Alzheimer's disease and osteoporosis, the estrogen industry is arguing that the problems are caused by a suddenly developing estrogen deficiency, rather than by prolonged exposure to estrogen.
某些类型的痴呆症，如阿尔茨海默氏病，涉及大脑的终身退化过程，并伴有炎症成分，这可能使它们与骨质疏松和肌肉萎缩相媲美。(在大脑中，与巨噬细胞类似的小胶质细胞和星形胶质细胞可以产生TNF。)当人们注意到经常服用阿司匹林的人患阿尔茨海默氏病的几率较低时，人们认识到了炎症过程在阿尔茨海默氏病中的重要性。阿司匹林可以抑制TNF的形成，而且已经发现阿司匹林可以延缓骨质流失。就骨质疏松症(A. murrilo - uribe, 1999)而言，与阿尔茨海默病一样，女性的发病率是男性的两到三倍。对于阿尔茨海默病和骨质疏松症，雌激素行业认为这些问题是由突然发展的雌激素缺乏引起的，而不是长期接触雌激素。
Similar arguments were made fifty years ago regarding the nature of the menopause itself–that it was caused by a sudden decrease in estrogen production. The evidence that has accumulated in the last forty years has decisively settled that argument: Menopause is the result of prolonged exposure to estrogen. (Even one large dose destroys certain areas in the brain, and chronic, natural levels damage the nerves that regulate the pituitary. Overactivity of the pituitary leads to many other features of aging.)
50年前，关于更年期本身的性质也有类似的争论——它是由雌激素分泌的突然减少引起的。在过去四十年中积累的证据已经明确地解决了这个争论:更年期是长期接触雌激素的结果。(即使是大剂量的剂量也会破坏大脑中的某些区域，而长期的、自然的剂量会损害调节脑垂体的神经。脑下垂体的过度活动会导致衰老的许多其他特征。)
The links between estrogen and TNF appear to be essential factors in aging and its diseases. Each of these substances has its constructive, but limited, place in normal physiology, but as excitatory factors, they must operate within the appropriate constraints. The basic constraint is that resources, including energy and oxygen, must be available to terminate their excitatory actions. Adequate oxygen, a generous supply of carbon dioxide, saturated fats, thyroid, and progesterone restrain TNF, while optimizing other cytokines and immune functions, including thymic protection. In the development of the organism and its adaptive functions, there are patterned processes, functional systems, that can clarify the interactions of growth and atrophy. The respiratory production of energy and carbon dioxide, and the respiratory defect in which lactic acid is produced, correspond to successful adaptation, and to stressful/excitotoxic maladaptation, respectively. Excitotoxicity, and Meerson's work on the protective functions of the antistress hormones, have to be understood in this framework. This framework integrates the understanding of cancer metabolism with the other stress metabolisms, and with the metabolism of normal growth.
雌激素和TNF之间的联系似乎是衰老及其疾病的重要因素。这些物质中的每一种都有其建设性的，但有限的地位，在正常生理，但作为兴奋因素，他们必须在适当的限制下运作。基本的限制是，包括能量和氧气在内的资源必须能够终止它们的兴奋性行为。充足的氧气、大量的二氧化碳、饱和脂肪、甲状腺和孕酮可以抑制TNF，同时优化其他细胞因子和免疫功能，包括胸腺保护。在生物的发展及其适应功能中，有一些模式化的过程和功能系统，它们可以阐明生长和萎缩的相互作用。能量和二氧化碳的呼吸生产，以及乳酸产生的呼吸缺陷，分别对应于成功的适应和应激/兴奋毒性不良适应。兴奋毒性，以及Meerson关于抗应激激素保护功能的工作，必须在这个框架中被理解。这个框架将癌症代谢与其他应激代谢以及正常生长代谢的理解结合起来。
Unsaturated fats, iron, and lactic acid are closely related to the actions and regulation of TNF, and therefore they strongly influence the nature of stress and the rate of aging.
不饱和脂肪、铁和乳酸与TNF的作用和调节密切相关，因此它们强烈影响应激的性质和衰老的速度。
The fact that cancer depends on the presence of polyunsaturated fats probably relates to the constructive and destructive actions of TNF: The destructive effects such as multiple organ failure/congestive heart failure/shock-lung, etc., apparently involve arachidonic acid and its metabolites, which are based on the so-called essential fatty acids. When oxygen and the correct nutrients are available, the hypermetabolism produced by TNF could be reparative (K. Fukushima, et al., 1999), rather than destructive. Stimulation in the presence of oxygen produces carbon dioxide, allowing cells to excrete calcium and to deposit it in bones, but stimulation in the absence of oxygen produces lactic acid and causes cellular calcium uptake.
癌症的事实取决于多不饱和脂肪的存在可能与肿瘤坏死因子的建设性和破坏性的行动:多器官功能衰竭等破坏作用/充血性心力衰竭/ shock-lung,等等,显然包括花生四烯酸及其代谢产物,这是基于所谓的必需脂肪酸。当氧气和正确的营养物质可用时，TNF产生的高代谢可能是修复性的(K. Fukushima，等，1999)，而不是破坏性的。在氧气存在的情况下刺激会产生二氧化碳，使细胞排出钙并将其沉积在骨骼中，但在氧气缺乏的情况下刺激会产生乳酸并导致细胞钙吸收。
It is in this context that the therapeutic effects of saturated fats, carbon dioxide, progesterone, and thyroid can be understood. They restore stability to a system that has been stimulated beyond its capacity to adapt without injury.
正是在这种背景下，饱和脂肪、二氧化碳、孕酮和甲状腺的治疗效果才得以理解。它们恢复了系统的稳定性，使系统受到的刺激超出了其无损伤适应能力。
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