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On average, women’s hemoglobin and hematocrit are both about 12% lower than men’s, with little change in the ratio with aging. This difference has been ascribed to the loss of blood by menstruation, despite the fact that female animals generally (the great majority of which don’t menstruate) also have a lower hemoglobin level than males. There is some evidence that estrogen slightly suppresses the formation of erythropoietin, the regulator of red blood cell formation, but most evidence indicates that it is estrogen’s suppression of the bone marrow itself that accounts for most of the difference. Some evidence indicates that water retention caused by estrogen is responsible for the blood dilution (Ueda,et al., 1986). 平均而言，女性的血红蛋白和红细胞压积都比男性低12%左右，随着年龄的增长，这一比例几乎没有变化。这种差异被归因于月经失血，尽管事实上雌性动物（绝大多数不月经）的血红蛋白水平也比雄性动物低。有一些证据表明，雌激素略微抑制红细胞生成的调节因子促红细胞生成素的形成，但大多数证据表明，雌激素对骨髓本身的抑制是造成这种差异的主要原因。一些证据表明，雌激素引起的水分滞留是血液稀释的原因（Ueda等人，1986年）。
Estrogen increases the stiffness of red blood cells and the viscosity of plasma (Solerte, et al., 1991), but women’s whole blood is less viscous than men’s (Kameneva, et al., 1999). This improved flowability of the blood, maintaining adequate oxygenation of tissues, results from the lower concentration of red cells. 雌激素会增加红细胞的硬度和血浆的粘度（Solerte等人，1991年），但女性的全血粘度低于男性（Kameneva等人，1999年）。这种血液流动性的改善，维持了组织的充足氧合，是红细胞浓度降低的结果。
For many years, this relative anemia of women led doctors to prescribe iron supplements for the correction of “iron deficiency anemia,” with no indication of an iron deficiency other than low hemoglobin and low hematocrit. That practice has had various harmful consequences. Those consequences of consuming more iron than is needed have never been adequately explored. 多年来，女性的这种相对贫血导致医生开铁剂补充剂来纠正“缺铁性贫血”，除了低血红蛋白和低红细胞压积外，没有任何缺铁的迹象。这种做法产生了各种有害后果。人们从未充分探讨过消费过多铁的后果。
> While osteoporosis and dementia involve iron overload, they are associated with an increased likelihood of anemia. 虽然骨质疏松症和痴呆症涉及铁超载，但它们与贫血的可能性增加有关。
While estrogen decreases the formation of blood, it increases the assimilation of iron from the diet, so that when a woman’s estrogen is high her extraction of iron from food is several times as high as a man’s. This increased affinity for iron can compensate for a greater need for iron resulting from menstrual blood loss and pregnancy, but it can also lead to the accumulation of toxic amounts of iron in the body if the diet supplies more than is needed. Both men and women accumulate iron with aging, and after menopause tissue iron increases more rapidly in women. 虽然雌激素减少血液的形成，但它增加了从饮食中吸收铁的能力，因此，当女性雌激素水平较高时，其从食物中提取的铁含量是男性的数倍。这种对铁的亲和力的增加可以弥补月经失血和怀孕导致的对铁的更大需求，但如果饮食供应超过需要，也会导致体内有毒铁的积累。随着年龄的增长，男性和女性都会积累铁，绝经后女性体内组织铁的增加速度更快。
It has been known for a long time that calcium deposits in tissues such as arteries are mixed with iron (Peltomaa, et al., 1992; Langheinrich, et al., 2009), but there has been surprisingly little work to understand the reason for the association. In the 1960s, Hans Selye did a series of experiments in which a combination of injected iron salts and local tissue irritation caused deposition of calcium in the irritated tissue, producing a sclerodermalike condition. If he treated the animals with vitamin E at the same time, the tissue didn’t calcify. Vitamin E protects polyunsaturated fats from oxidation by iron, so the implication was that lipid peroxidation catalyzed by iron, triggered by slight stresses, was responsible for the tissue calcification. 长期以来，人们已经知道，动脉等组织中的钙沉积与铁混合（Peltoma等人，1992；Langhinrich等人，2009年），但令人惊讶的是，很少有研究能够理解这种关联的原因。在20世纪60年代，Hans Selye进行了一系列实验，其中注射的铁盐和局部组织刺激的组合导致受刺激组织中钙的沉积，从而产生类似硬皮病的情况。如果他同时用维生素E治疗动物，组织就不会钙化。维生素E保护多不饱和脂肪免受铁的氧化，因此这意味着由铁催化的脂质过氧化，由轻微的应力触发，是组织钙化的原因。
> Four day exposure of rats to hypoxia (10% O(2)) increased the level of lipofuscin-like pigments in erythrocytes up to 9 fold. This increase was completely prevented when the animals were exposed to hypercapnia (4.3% CO(2)) in addition to hypoxia. –Skoumalová, et al. 大鼠暴露于缺氧（10%O（2））四天后，红细胞中脂褐素样色素的水平增加了9倍。当动物暴露于高碳酸血症（4.3%CO（2））和缺氧时，这种增加被完全阻止。
Until the 1960s, a paralytic disease occurring in some western Pacific Ocean islands, “amyotrophical lateral sclerosis/parkinsonismdementia complex,” was believed to be caused by heredity, and then it was thought to be caused by a virus transmitted by cannibalism, later by aluminum poisoning, and then by poison from a toxin in blue-green algae. Starting in 1976, a series of studies found that all of the affected areas, from western New Guinea to southern Japan, with a variety of cultural practices and diets, had in common a nutritional deficiency of calcium, because of the water and soil in the region. Their soils also contained a high level of aluminum. 直到20世纪60年代，西太平洋一些岛屿上发生的一种麻痹性疾病“肌萎缩侧索硬化症/帕金森综合征”被认为是由遗传引起的，然后被认为是由食人传播的病毒引起的，后来又被认为是铝中毒，然后是蓝绿藻毒素的毒液。从1976年开始，一系列研究发现，从新几内亚西部到日本南部的所有受影响地区，由于该地区的水和土壤，有着各种各样的文化习俗和饮食习惯，都普遍存在钙营养不足的问题。他们的土壤也含有高水平的铝。
When calcium is deficient, secretion of parathyroid hormone increases, removing calcium from bones to meet the regulatory needs of the rest of the body. This involves suppressing oxidative metabolism that produces CO2, and partially replacing it with glycolytic metabolism, producing lactic acid. When lactic acid is formed by a cell, the interior of the cell becomes more alkaline,causing the structural proteins to be more negatively charged. This can lead to an increase of positively charged metal ions inside cells. When metals other than calcium, such as aluminum, iron, or lead, are abundant in food and water, these will be accumulated in cells along with calcium, where they will—in proportion to the unsaturation of the cell’s lipids—accelerate the processes of lipid peroxidation. The type of degenerative disease a person develops will depend partly on the types of metal and fat that accumulate in the tissues. 当钙缺乏时，甲状旁腺激素的分泌增加，从骨骼中清除钙以满足身体其他部位的调节需要。这包括抑制产生二氧化碳的氧化代谢，并用糖酵解代谢部分取代它，产生乳酸。 当细胞形成乳酸时，细胞内部变得更碱性，导致结构蛋白带更多负电。这会导致细胞内带正电的金属离子增加。当除钙以外的金属，如铝、铁或铅，在食物和水中含量丰富时，这些金属将与钙一起在细胞中积累，并与细胞脂质的不饱和度成比例，加速脂质过氧化过程。一个人患上的退行性疾病的类型在一定程度上取决于组织中积累的金属和脂肪的类型。
Women, under the effects of estrogen, accumulate (and synthesize) more of the extremely unsaturated fatty acids, such as DHA, than men do (Giltay, et al., 2004). 在雌激素的作用下，女性比男性积累（和合成）更多的极不饱和脂肪酸，如DHA（Giltay等人，2004年）。
At birth, the brain contains a considerable amount of highly unsaturated fats, mainly of the omega-9 series, which our bodies can synthesize from sugar or saturated fats. The placenta normally functions as a barrier against highly unsaturated fatty acids from foods. The fats in the mother’s diet enter her milk, with the result that the less stable omega-6 and omega-3 fats begin to accumulate in the breast-fed baby’s tissues, especially the brain; if it receives a formula “enriched” with iron and DHA, the process is likely to be accelerated. Steady growth during childhood dilutes these environmental factors, but as growth slows their concentration increases. The result is an increasing tendency to produce lipid peroxides, that damage proteins and nucleic acids, causing progressive loss of function and increased calcification. 出生时，大脑含有相当数量的高度不饱和脂肪，主要是欧米茄-9系列，我们的身体可以从糖或饱和脂肪中合成。胎盘通常起到屏障作用，防止食物中的高度不饱和脂肪酸。母亲饮食中的脂肪进入她的乳汁，导致较不稳定的ω-6和ω-3脂肪开始在母乳喂养婴儿的组织中积累，特别是大脑；如果它接受一种富含铁和DHA的配方奶粉，这个过程可能会加快。儿童时期的稳定生长稀释了这些环境因素，但随着生长放缓，这些环境因素的浓度会增加。 结果是产生脂质过氧化物的趋势增加，脂质过氧化物破坏蛋白质和核酸，导致功能逐渐丧失和钙化增加。
The presence of free, unbound iron in the tissues or in baby formula will degrade vitamin E, increasing the peroxidation of polyunsaturated fats. There are situations in which iron supplementation, without adequate vitamin E, can increase premature birth, increase the risk of hemolytic anemia in the newborn, and increase the risk of retinal damage (Johnson, et al., 1982; Henderson and Torch, 1976; Casanueva and Viteri, 2003). 组织或婴儿配方奶粉中的游离未结合铁会降解维生素E，增加多不饱和脂肪的过氧化作用。在某些情况下，补充铁而没有足够的维生素E，会增加早产，增加新生儿溶血性贫血的风险，并增加视网膜损伤的风险（Johnson，et al.，1982；亨德森与火炬，1976年；Casanueva和Viteri，2003年）。
Some of the products of lipid peroxidation, interacting with iron and other cell materials, become the very complexly structured age pigment, lipofuscin. Among the substances in these dark granules are some heme molecules, protected against elimination, which can catalyze the conversion of oxygen to water, without producing usable energy; the pigment becomes a drain on fuel and oxygen, creating a constant reductive, oxygen deficient, stress. This tendency to reduce oxygen contributes to the formation of vicious circles, inducing hypoxia inducible factor, HIF, which is a crucial factor in promoting iron absorption, and which activates many potentially dangerous enzymes, including heme oxygenase, HO, which turns heme groups into free iron, carbon monoxide, and bilirubin. HIF also activates aromatase, increasing estrogen (Samarajeewa, et al., 2013). 脂质过氧化的一些产物与铁和其他细胞物质相互作用，形成结构非常复杂的老年色素脂褐素。在这些暗颗粒中的物质中有一些血红素分子，可以防止消除，它可以催化氧转化为水，而不产生可用的能量；这种色素会消耗燃料和氧气，造成持续的还原性缺氧压力。 这种减少氧气的趋势有助于形成恶性循环，诱导缺氧诱导因子HIF，它是促进铁吸收的关键因素，并激活许多潜在危险的酶，包括血红素加氧酶HO，它将血红素基团转化为游离铁、一氧化碳和胆红素。HIF还激活芳香化酶，增加雌激素（Samarajeewa等人，2013年）。
About 60% of newborn babies are jaundiced for a few days, showing that the stress of being born has activated their HO, turning heme into its toxic components. The presence of free bilirubin is known to be associated with lipid peroxidation and DNA damage (Basu, et al. 2014). Better prenatal conditions would probably reduce the incidence of neonatal jaundice and stress, and this might involve avoidance of highly unsaturated fats and large iron supplements, and avoiding stressful medical procedures. 大约60%的新生儿几天内出现黄疸，这表明出生的压力激活了他们的血红素，将血红素转化为有毒成分。已知游离胆红素的存在与脂质过氧化和DNA损伤有关（Basu等，2014）。更好的产前条件可能会降低新生儿黄疸和压力的发生率，这可能包括避免高不饱和脂肪和大量补充铁，以及避免压力大的医疗程序。
Stresses that increase exposure to excess iron and PUFA can shorten the life span of red blood cells, adding to the burden of heme and lipid peroxides. The well known association of the autoimmune diseases with excessive estrogen probably involves the increases of hypoxia, HIF, HO, iron, and PUFA under the influence of estrogen. Aldehydes produced by the breakdown of fats react with cell proteins, making them antigenic, while episodes of hypoxia and hypoglycemia make the immune system more reactive. 增加暴露于过量铁和多不饱和脂肪酸的压力会缩短红细胞的寿命，增加血红素和脂质过氧化物的负担。众所周知，自身免疫性疾病与过量雌激素的关系可能涉及在雌激素影响下缺氧、HIF、HO、铁和PUFA的增加。脂肪分解产生的醛类与细胞蛋白发生反应，使其具有抗原性，而缺氧和低血糖的发作使免疫系统更具反应性。
All microorganisms require iron to grow, so limiting the availability of iron will limit their ability to be infective. Our respiratory and digestive membranes secrete two proteins, lactoferrin and transferrin, which have a very high affinity for iron atoms, as well as other germicidal properties, and provide a first defense against infection. Milk contains these proteins, which provide anti-infective protection for the baby, while letting it safely assimilate iron by delivering it directly to proteins on the surface of the intestine that bind it. Since cancer cells’ growth is stimulated by iron, the circulation of these iron-binding proteins in the blood and body fluids probably forms part of our defense against metastasis. 所有微生物都需要铁来生长，因此限制铁的可用性将限制它们的感染能力。我们的呼吸和消化膜分泌两种蛋白质，乳铁蛋白和转铁蛋白，这两种蛋白质对铁原子有很高的亲和力，以及其他杀菌特性，并对感染提供第一道防御。牛奶中含有这些蛋白质，它们为婴儿提供抗感染保护，同时通过将铁直接输送到与铁结合的肠道表面的蛋白质中，让婴儿安全地吸收铁。由于癌细胞的生长受到铁的刺激，这些铁结合蛋白在血液和体液中的循环可能是我们抵抗转移的一部分。
Another type of anti-microbial peptide (the cathelicidins and hepcidin) is able to kill viruses and bacteria directly, without binding iron. Hepcidin was discovered in the urine, and it’s important for preventing bladder infections. Synthesis of the cathelicidins is dependent on vitamin D. 另一种类型的抗菌肽（cathelicidins和hepcidin）能够直接杀死病毒和细菌，而不与铁结合。在尿液中发现了Hepcidin，它对预防膀胱感染很重要。cathelicidins的合成依赖于维生素D。
One of the ways in which estrogen increases iron retention is by inhibiting the formation of hepcidin (Balbouj, et al., 2018), since one of hepcidin’s main functions is to limit the absorption of iron from the intestine, and to inhibit its release into the bloodstream. Progesterone increases the synthesis of hepcidin (Xiang, et al., 2016). 雌激素增加铁潴留的一种方式是通过抑制hepcidin的形成（Balbouj等，2018），因为hepcidin的主要功能之一是限制铁从肠道的吸收，并抑制其释放到血液中。
At the beginning of menopause, ovarian production of progesterone is suddenly interrupted, while the production of estrogen in fat, skin, muscles, and other tissues increases. Following menopause, the bones as well as the brain accumulate iron, and the effects include a much higher risk of osteoporosis and Alzheimer’s disease in women than in men. While osteoporosis and dementia involve iron overload, they are associated with an increased likelihood of anemia. 更年期开始时，卵巢孕酮的分泌突然中断，而脂肪、皮肤、肌肉和其他组织中雌激素的分泌增加。 绝经后，骨骼和大脑都会积累铁，其影响包括女性患骨质疏松症和阿尔茨海默病的风险比男性高得多。 虽然骨质疏松症和痴呆症涉及铁超载，但它们与贫血的可能性增加有关。
The increase of tissue iron in aging is a factor in the greater susceptibility to infection. Iron not only supports the growth of infective organisms, but increases the formation of inflammatory cytokines and weakens the barrier function of the intestine, contributing to endotoxemia (Visitchanakun, et al., 2020). These factors are involved in the corona virus sickness, and iron overload is increasingly recognized as a factor in susceptibility to that infection and in its main characteristics, extreme inflammation, the cytokine storm, and hyper-coagulability. Removal of the iron by chelation has been proposed to reduce the inflammation and coagulation (Vlahakos, et al., 2021; Perricone, et al., 2020; Edeas, et al., 2020; Nielsen and Pretorius, 2020). Commonly used chelators can move harmful metals from the bones, where they were inactive, into the brain and kidneys; some chelators taken orally can move metals from the intestine into the mitochondria. Lactoferrin, currently being tested, seems to be safer, and besides reducing free iron it is antiinflammatory, reducing iron absorption, while blocking viral infection in multiple ways (Habib, et al., 2021; Campione, et al., 2021). 衰老过程中组织铁含量的增加是感染易感性增加的一个因素。 铁不仅支持感染性有机体的生长，而且增加炎性细胞因子的形成，削弱肠道的屏障功能，导致内毒素血症（Visitchanakun等人，2020年）。 这些因素与冠状病毒病有关，铁超载越来越被认为是感染易感性的一个因素，其主要特征是极端炎症、细胞因子风暴和高凝。通过螯合作用去除铁可以减少炎症和凝血（Vlahakos等人，2021；Perricone等人，2020年；Edeas等人，2020年；尼尔森和普雷托里厄斯，2020年）。 常用的螯合剂可以将不活跃的有害金属从骨骼转移到大脑和肾脏；一些口服螯合剂可以将金属从肠道转移到线粒体中。目前正在测试的乳铁蛋白似乎更安全，除了减少游离铁外，它还具有抗炎作用，减少铁的吸收，同时以多种方式阻止病毒感染（Habib等，2021；Campione等人，2021年）。
The long history of prescribing iron pills to women, regardless of their diet, has created a culture that has little interest in considering the harmful effects of excess iron. That attitude exists within the fraudulent “science” tradition created and sustained in the last 80 years by the estrogen industry that, to create a market for their product, has identified menopause and old age as a time of estrogen deficiency. 长期以来，无论女性的饮食如何，都给她们开铁片，这造就了一种文化，这种文化对考虑过量铁的有害影响几乎没有兴趣。这种态度存在于过去80年中由雌激素行业创造和维持的欺诈性“科学”传统中，该行业为了为其产品创造市场，将绝经和老年视为雌激素缺乏的时期。
The fact that unopposed estrogen contributes to a toxic accumulation of iron, and promotes the retention of highly unsaturated fats (forming lipofuscin) in the brain and other organs, degrading immunity, brain function, and bone strength, gives us numerous opportunities to intervene to remedy and to prevent some serious health problems, including those that have been thought to be inevitable consequences of aging. 非对抗性雌激素会导致铁的毒性积累，并促进高度不饱和脂肪（形成脂褐素）在大脑和其他器官中的滞留，降低免疫力、大脑功能和骨骼强度，这一事实为我们提供了许多干预治疗和预防某些严重健康问题的机会，包括那些被认为是老龄化不可避免的后果。
When we act to correct one part of this interlocking system, we are usually improving other things as well. For example, estrogen’s effect on hepcidin that increases iron can be reversed by increased progesterone, with its opposite effect on hepcidin (Xiang, et al., 2016), while estrogen’s effect on intracellular calcium is also reversed by progesterone (Luoma, et al., 2012; Xu, et al., 2005; Zhang, et al., 2002). 当我们采取行动纠正联锁系统的一部分时，我们通常也在改进其他方面。例如，增加孕酮可以逆转雌激素对铁蛋白的作用，增加铁蛋白的作用与对铁蛋白的作用相反（Xiang等人，2016），而孕酮也可以逆转雌激素对细胞内钙的作用（Luoma等人，2012；徐等，2005年；张等人，2002年）。
Besides progesterone, two other steroids cause an increase of hepcidin—epitiostanol, an anti-estrogen used to treat breast cancer, and mifepristone, which antagonizes cortisol as well as estrogen and progesterone. The importance of non-toxic substances to lower iron is widely recognized: “Small molecules capable of inducing hepcidin could also be of great therapeutic benefit to patients with hemochromatosis or other disorders complicated by iron overload, such as β-thalassemia. Unfortunately, there has been limited progress in identifying small molecules that increase hepcidin biosynthesis” (Xiang, et al., 2016). 除黄体酮外，还有两种类固醇会导致用于治疗乳腺癌的抗雌激素药物hepcidin epiostatol和米非司酮（对抗皮质醇以及雌激素和黄体酮）的增加。无毒物质对降低铁的重要性已得到广泛认可：“能够诱导hepcidin的小分子对血色素沉着症或其他伴有铁超载的疾病（如β-地中海贫血）的患者也有很大的治疗益处。 不幸的是，在识别增加hepcidin生物合成的小分子方面进展有限”（Xiang等人，2016）。
Oxidative metabolism is the basic factor in resisting the degenerative processes; for example, the CO2 that the mitochondria produce prevents iron toxicity in a variety of ways. It inhibits the formation of lactic acid, eliminating that cause of iron and calcium deposition in cells, and it acts directly on iron to make it less toxic; for example it stabilizes lysosomes (Gerby, et al., 2019), and reduces the activity of free radicals produced by lipid peroxidation, reducing formation of lipofuscin (Skoumalová, et al., 2008). One of its effects is probably by stabilizing transferrin, increasing its affinity for iron: “It was found that hypercapnia in vivo protects against the damaging effects of ischemia or hypoxia. Several mechanisms have been suggested to explain the protective role of CO2 in vivo. The most significant appears to be stabilization of the iron-transferrin complex which prevents the involvement of iron ions in the initiation of free radical reactions” (Veselá & Wilhelm, 2002). 氧化代谢是抵抗退化过程的基本因素；例如，线粒体产生的二氧化碳以多种方式防止铁中毒。它抑制乳酸的形成，消除细胞内铁和钙沉积的原因，并直接作用于铁，使其毒性降低；例如，它稳定溶酶体（Gerby等人，2019年），降低脂质过氧化产生的自由基活性，减少脂褐素的形成（Skoumalová等人，2008年）。其作用之一可能是稳定转铁蛋白，增加其对铁的亲和力：“研究发现，体内高碳酸血症可防止缺血或缺氧的破坏性影响。 已经提出了几种机制来解释二氧化碳在体内的保护作用。 最重要的似乎是铁转铁蛋白复合物的稳定化，它阻止铁离子参与自由基反应的启动”（Veselá26 Wilhelm，2002）。
Because of the close interaction between iron and calcium, vitamin D and adequate calcium in the diet are important for protection against chronic iron overload (Esparragoza, et al., 2020; Lee, et al., 2021). In general, avoiding foods with added iron is good, and having coffee or tea with naturally iron rich foods is protective for most people. Even during pregnancy, slightly low hemoglobin isn’t enough to justify using an iron supplement—slightly low hemoglobin is protective against infections and stress. Very low serum ferritin and transferrin saturation are reasonable indicators of low tissue iron stores. 由于铁和钙之间的密切相互作用，饮食中的维生素D和足够的钙对于防止慢性铁超载非常重要（Esparagoza等，2020；李等人，2021年）。一般来说，避免吃额外添加铁的食物是好的，喝含有天然富含铁的食物的咖啡或茶对大多数人都有保护作用。即使在怀孕期间，稍微低的血红蛋白也不足以证明使用铁补充剂的合理性。稍微低的血红蛋白可以防止感染和压力。极低的血清铁蛋白和转铁蛋白饱和度是低组织铁储备的合理指标。
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