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褪黑激素 镁 抗癌与疫苗解毒
Melatonin, magnesium, anti-cancer effects, and vaccine detoxification

https://open.substack.com/pub/amandakingnd/p/the-dark-hormone-rising-high-dose?selection=705b3074-2098-4d98-a0e7-ea8151b9ccc9

Finally, melatonin is also an oncostatic molecule.
Oncostatic means ‘Anti-Cancer’.

最後，褪黑激素也是一種腫瘤抑菌分子。

Oncostatic的意思是「抗癌」。

(For a discussion about the Heart Health implications - see comments below)
Many of us know it as the supplement that regulates our sleep cycle after a long haul flight and at its most simplest, Melatonin is known as the Master Sleep Hormone… but we now know it does so much more than just help us to sleep.
Melatonin is a Chronobiotic (love this word). This means it regulates a gene in the part of our brain (SCN - suprachiasmatic nucleus) responsible for our circadian rhythm… that gene just happens to be called CLOCK! It regulates our internal clocks across organs and down to our cells, everything has its rhythm.

It has been compared to Vitamin D as they are both hormones. Vitamin D deficiency happens when we don’t get enough light and Melatonin deficiency happens when we don’t get enough dark. Specifically because we are wildly over-exposed to blue light from screens.

Melatonin is actually made from Serotonin, our happy hormone. Sunshine is serotonergic (it makes serotonin). This leads us to the logical connection between getting enough daylight (making serotonin) and sleeping well (converting it to melatonin).
Melatonin is anti-inflammatory, it’s a powerful antioxidant and it protects our healthy mitochondria and there’s more… it protects neurons - our nerve cells from oxidative stress and that reduces our chances of developing diseases of neuro-degeneration like Parkinson’s or Alzheimer’s diseases. Melatonin regulates our immune system, it modulates oxidative stress (note that this doesn’t mean it works solely as an ‘anti-oxidant’). It keeps Redox balanced - To learn more about Redox read my last post….

Research into cancer as a metabolic disease has gathered pace over the last few years, so we have been able to identify various mechanisms or pathway by which cancer develops, grows and adapts. This understanding has led to an explosion of recent research to try isolate drugs, supplements and therapies that interrupt those mechanisms in attempt to thwart cancer metabolism.

Circadian rhythm disruption can be regarded as a carcinogen. In 2007, the International Agency for Research on Cancer (IARC) classified shift work that involves circadian disruption as probably carcinogenic to humans. Night-shift workers have higher risks of breast cancer, rectal cancer and lung cancer.

Melatonin & Cancer
In my Nutrigenomics Practitioner training in 2023, I remember learning about the gene MTNR1B - for Melatonin. We learned that if this gene was mutated and downregulated (slower) it meant that person was less reactive to the same amount of melatonin. This is actually a diabetes risk and the reason why is that if a person with this SNP (singular nucleotide polymorphism) or mutation, eats food before bed, which let’s face it, lots of people do regularly, then they don’t secrete adequate levels of insulin to bring down the blood sugar from the meal. This is because due to the SNP, their pancreas and liver don’t respond properly to melatonin. That leads over time to blood sugar dysregulation and insulin resistance which can lead to Type 2 Diabetes.

Many cancers use these melatonin pathways for growth. We see altered melatonin signalling in many cancers, depending on the tumor type. We see increased MT1 in breast cancer cells. Higher MT1 and MT2 in squamous cell carcinoma. People with SNPs on MT1 and MT2 were more likely to develop HCC (Liver Cancer).
It sounds a little counterproductive doesn’t it?
If Cancers use the melatonin pathways to grow, then surely supplementation of melatonin would be like throwing fuel on a bonfire…. right?
Wrong! and here’s why…
Imagine lots of MT1 (melatonin) receptors on a cell - each receptor is a bit like a docking station, a parking space or an open door. Your supplemental melatonin gives you millions of molecules of melatonin and each one sits in a docking port, parks in the parking space or shuts the door. It blocks these receptors which blocks the growth pathway by occupying the space. This has the effect of hitting the OFF switch on cancer growth. All this takes place overnight while your healthy cells also benefit from immune system regulation, better sleep and restoration- so vital to your recovery, nervous system benefits and protection of your healthy mitochondria.

The anti cancer effects of melatonin
Inhibits Cancer Growth
Cells go through a series of steps to make copies of themselves (cell division). The process is arrested or stopped at a stage called G0/G1 which is the part where cells start to prepare to divide. At this stage of cell cycle arrest, cancer cell replication is nipped in the bud. That’s because melatonin suppresses Cyclins which are proteins that are usually involved in the characteristic uncontrolled proliferation of cancer. Melatonin also inhibits CDK which is a target in conventional medicine for many drugs like pabociclib and ribociclib in breast cancer and sorafenib in liver and thyroid cancer.

Increases Cancer Apoptosis (cell suicide)
Melatonin activates apoptosis but this is where it gets super interesting. Usually we think of ROS mediated cell death - where radical oxygen species or free radicals are created in the cell that lead to its destruction. It was found that this DID happen with melatonin, but there was something else that we don’t understand yet, going on too. We know this because when antioxidants like glutathione were brought in to neutralise the ROS (to protect the cell from death), when cancer was exposed to melatonin, cancer cells died anyway, regardless of the antioxidants present and we don’t know how…
Suppressed Angiogenesis
We definitely want anything that can slow down angiogenesis in our cancer protocol. Angiogenesis is the process whereby cancer cell signals to have small vessels grow in the body to bring them supplies for tumor growth. These signals are called VEGF and HIF1A for example. Melatonin suppresses cancer cell signalling and this stops the tumor-driven, blood vessel formation process. This halts migration, invasion and metastases of breakaway tumor cells.
Immune System
So many things to love about melatonin’s effects on the immune system. It wakes up our anti-tumor immune surveillance team and it increases cancer-toxic T cells.

Some very interesting developments with melatonin and immunotherapy are being shown in preclinical research too. Melatonin has been shown to down regulate PD-L1 expression. PD-L1 = Programmed Death Ligand. PD-L1 can slow down the cancer-toxic T cells in our immune system but melatonin distracts PD-L1 - letting our biological army do its job! This is also what immunotherapies like Pembrolizumab do, which makes melatonin an interesting prospect as a future player alongside immunotherapy.

What “high-dose” melatonin actually means
As many of my patients will have heard me say, I only recommend dosing to levels that I have personally seen the data on. With melatonin, there isn’t enough research or any agreed definition yet on daily dosing up to levels like 120mg. Some protocols may go even as high as 180mg.
We do know that the anti cancer mechanisms we seek do not happen at basic dosing for jet lag for example. 0.5-5mg is commonly recommended to help people restore a natural circadian rhythm but much higher doses are seen for anti-cancer effects in integrative oncology.
When it comes to higher dosing, we have seen that increased tumor stress along with protection of healthy cells happen in a dose dependent manner. The more melatonin, the more effects. Many studies were done on mice at dosing up to 200mg human equivalent a day, but mouse metabolism runs 7 times faster than yours. More is not necessarily better. We would be wise to look at the dosing from research on humans first.
In research on humans, doses of melatonin tend to be around 20-60mg a night. So in my protocols I personally only recommend supplementation up to 60mg nightly - titrated up slowly. Research shows us that we get the anti-cancer effects we want from these levels of melatonin. Preferentially extended release where possible and avoid all B6 supplements when you have cancer, you might find B6 in your melatonin supplement, this should be stopped if it is in yours and you should find another supplement.
It is generally recommended to have much higher doses as a one off prior to radioactive imaging scans but speak with your integrative practitioner to find out how to protect your body from the ionozing radiation in PET/CT Scans with melatonin.
There can be some short-term side effects from high-dose melatonin including, daytime drowsiness, dizziness and headaches.
Melatonin can interact with anti-coagulants, sedatives and immunomodulatory drugs. Always speak with your practitioner before you bring any supplements into your regime.

Cancer types with strongest supportive signals
Breast cancer
The data on BRCA1 mutated Estrogen positive cancer is very encouraging. “Expression of BRCA-1, p53, p21(WAF) and c-myc were up-regulated by estradiol. Treatment of the stimulated cells with melatonin counteracted the increase induced by estradiol almost completely” This means that estrogen caused increased growth and metastatic potential in breast cancer cells, effectively triggering the cancer process. Exposing those same cells to melatonin almost entirely stopped that process.
Melatonin inhibited breast cancer cell invasion in one study, reducing the chance of developing metastases.
Lung Cancer
Those that had increased cancer activity in lung cancer tended to have lower expression on melatonin receptors while increasing the expression resulted in slower tumor growth. What ‘expression’ means is that the higher it is, the more doors of opportunity for melatonin to jump into and occupy, blocking the pathway to progression of lung cancer in people who supplement melatonin.
Liver cancer (HCC)
It was found that people with decreased sensitivity on melatonin genes/receptors (MTNR1B) were more at risk of HCC liver cancer. (Su et al., 2017)
A combination of Melatonin and Sorafenib both decreased liver cancer proliferations genes AKT, CDK4/6 and cMyc which is associated with increased invasion and metastases.
Squamous Cell Carcinoma
In oral SCC it was also found that the more receptors for MT1, the increased susceptibility to the anti-cancer effects of melatonin.
Final word
Melatonin isn’t a miracle cure but it’s a serious contender in the integrative oncology sphere. It should be taken seriously as an anti-cancer agent and while we don’t have the human trials yet, the preclinical and current research is very promising. I particularly love that it supports healthy cells and suppresses cancer metabolism whilst promoting healthy, restful sleep, so integral to healing.

Cancer types with strongest supportive signals
Breast cancer
The data on BRCA1 mutated Estrogen positive cancer is very encouraging. “Expression of BRCA-1, p53, p21(WAF) and c-myc were up-regulated by estradiol. Treatment of the stimulated cells with melatonin counteracted the increase induced by estradiol almost completely” This means that estrogen caused increased growth and metastatic potential in breast cancer cells, effectively triggering the cancer process. Exposing those same cells to melatonin almost entirely stopped that process.
Melatonin inhibited breast cancer cell invasion in one study, reducing the chance of developing metastases.
Lung Cancer
Those that had increased cancer activity in lung cancer tended to have lower expression on melatonin receptors while increasing the expression resulted in slower tumor growth. What ‘expression’ means is that the higher it is, the more doors of opportunity for melatonin to jump into and occupy, blocking the pathway to progression of lung cancer in people who supplement melatonin.
Liver cancer (HCC)
It was found that people with decreased sensitivity on melatonin genes/receptors (MTNR1B) were more at risk of HCC liver cancer. (Su et al., 2017)
A combination of Melatonin and Sorafenib both decreased liver cancer proliferations genes AKT, CDK4/6 and cMyc which is associated with increased invasion and metastases.
Squamous Cell Carcinoma
In oral SCC it was also found that the more receptors for MT1, the increased susceptibility to the anti-cancer effects of melatonin.
Final word
Melatonin isn’t a miracle cure but it’s a serious contender in the integrative oncology sphere. It should be taken seriously as an anti-cancer agent and while we don’t have the human trials yet, the preclinical and current research is very promising. I particularly love that it supports healthy cells and suppresses cancer metabolism whilst promoting healthy, restful sleep, so integral to healing.

褪黑激素 镁 抗癌与疫苗解毒

在2023年的營養基因組學從業者培訓中，我記得我學習了MTNR1B基因——用於褪黑激素。 我們瞭解到，如果該基因突變並下調（較慢），這意味著該人對相同量的褪黑激素的反應較差。 這實際上是一種糖尿病風險，原因是如果一個患有SNP（單核苷酸多型性）或突變的人在睡覺前進食，讓我們面對現實吧，很多人經常這樣做，那麼他們沒有分泌足夠的胰島素來降低膳食中的血糖。 這是因為由於SNP，他們的胰腺和肝臟對褪黑激素反應不正常。 隨著時間的推移，這會導致血糖失調和胰島素抵抗，從而導致2型糖尿病。

它被比作維生素D，因為它們都是激素。 當我們沒有得到足夠的光線時，就會出現維生素D缺乏，當我們沒有得到足夠的黑暗時，就會發生褪黑蛋白缺乏。 特別是因為我們過度暴露在螢幕的藍光下。

褪黑激素實際上是由血清素製成的，血清素是我們的快樂荷爾蒙。 陽光是血清素能（它能製造血清素）。 這引導我們找到獲得足夠的日光（製造血清素）和睡個好覺（將其轉換為褪黑激素）之間的邏輯聯絡。

褪黑激素是抗炎的，它是一種強大的抗氧化劑，它保護我們健康的線粒體，還有更多......它保護神經元——我們的神經細胞免受氧化應激，從而減少我們患帕金森病或阿爾茨海默病等神經退行性疾病的機率。 褪黑激素調節我們的免疫系統，它調節氧化應激（請注意，這並不意味著它僅作為「抗氧化劑」發揮作用）。 它保持氧化還原平衡-要了解更多關於氧化還原的資訊，請閱讀我上一篇文章......

在過去的幾年裡，對癌症作為一種代謝性疾病的研究加快了步伐，因此我們已經能夠確定癌症發展、生長和適應的各種機制或途徑。 這種理解導致最近研究激增，試圖分離藥物、補充劑和療法，以中斷這些機制，試圖阻止癌症代謝。

晝夜節律紊亂可以被視為致癌物。 2007年，國際癌症研究機構（IARC）將涉及晝夜紊亂的輪班工作歸類為可能對人類致癌。 夜班工人患乳腺癌、直腸癌和肺癌的風險更高。

許多癌症使用這些褪黑激素途徑來生長。 根據腫瘤型別，我們看到許多癌症的褪黑激素訊號傳遞發生了變化。 我們看到乳腺癌細胞中的MT1增加。 鱗狀細胞癌的MT1和MT2較高。 MT1和MT2上SNP的人更有可能患上HCC（肝癌）。

這聽起來有點適得其反，不是嗎？

如果巨蟹座使用褪黑激素途徑生長，那麼補充褪黑激素肯定就像在篝火上扔燃料一樣......對嗎？

錯了！ 原因如下......

想象一下，細胞上有很多MT1（褪黑激素）受體——每個受體都有點像對接站、停車位或開啟的門。 你的補充褪黑激素給你數百萬分子的褪黑激素，每個分子都坐在對接埠上，停在停車位或關門。 它阻斷這些受體，這些受體透過佔據空間來阻斷生長途徑。 這對癌症生長有關閉開關的作用。 所有這些都在一夜之間發生，而你的健康細胞也受益於免疫系統調節、更好的睡眠和恢復——這對你的恢復、神經系統有益和保護健康線粒體至關重要。

褪黑激素的抗癌作用

抑制癌症的生長

細胞要經歷一系列步驟來複製自己（細胞分裂）。 這個過程在一個叫做G0/G1的階段被停止或停止，G0/G1是細胞開始準備分裂的部分。 在細胞週期停止的這個階段，癌細胞複製在萌芽中被扼殺。 這是因為褪黑激素抑制了週期蛋白，週期蛋白是通常參與癌症特徵不受控制擴散的蛋白質。 褪黑激素還抑制CDK，CDK是傳統醫學中許多藥物的靶點，如乳腺癌的pabociclib和ribociclib以及肝癌和甲狀腺癌的sorafenib。

增加癌症細胞凋亡（細胞自殺）

褪黑激素啟動細胞凋亡，但這就是它變得超級有趣的地方。 我們通常想到的是ROS介導的細胞死亡——在細胞中產生自由基氧種或自由基，導致其破壞。 發現這確實發生在褪黑激素身上，但還有一些我們還不明白的事情，也在發生。 我們知道這一點是因為當谷胱甘肽等抗氧化劑被引入中和ROS（保護細胞免受死亡）時，當癌症暴露在褪黑激素中時，癌細胞無論如何都會死亡，無論存在什麼抗氧化劑，我們不知道如何......

抑制血管生成

在我們的癌症方案中，我們絕對想要任何可以減緩血管生成的東西。 血管生成是癌細胞發出訊號，使小血管在體內生長，為腫瘤生長帶來供應的過程。 例如，這些訊號被稱為VEGF和HIF1A。 褪黑激素抑制癌細胞訊號，這阻止了腫瘤驅動的血管形成過程。 這阻止了分離腫瘤細胞的遷移、入侵和轉移。

免疫系統

褪黑激素對免疫系統的影響有很多值得喜愛的地方。 它喚醒了我們的抗腫瘤免疫監測團隊，並增加了對癌症毒性的T細胞。

褪黑激素和免疫療法的一些非常有趣的發展也在臨床前研究中得到展示。 褪黑激素已被證明可以降低PD-L1表達的調節。 PD-L1 = 程式化死亡結合。 PD-L1可以減緩我們免疫系統中的致癌T細胞，但褪黑激素會分散PD-L1的注意力——讓我們的生物軍隊做它的工作！ 這也是像彭布羅利珠單抗這樣的免疫療法的作用，這使得褪黑激素成為與免疫療法並列的未來參與者的有趣前景。

「高劑量」褪黑激素到底是什麼意思

正如我的許多患者會聽到我所說，我只建議將劑量劑量到我個人看到的資料水準。 對於褪黑激素，對於每天的劑量高達120毫克，還沒有足夠的研究或任何商定的定義。 一些協議甚至可能高達180毫克。

我們確實知道，例如，我們尋求的抗癌機制不會在時差的基本劑量下發生。 通常建議使用0.5-5mg來幫助人們恢復自然的晝夜節律，但在綜合腫瘤學中，抗癌效果的劑量要高得多。

當談到更高的劑量時，我們已經看到腫瘤壓力的增加以及對健康細胞的保護以劑量依賴的方式發生。 褪黑激素越多，效果就越多。 對小鼠進行了許多研究，每天劑量高達200毫克的人類當量，但小鼠的新陳代謝比你的快7倍。 更多不一定更好。 我們最好先看看人類研究的劑量。

在對人類的研究中，褪黑激素的劑量通常在每晚20-60毫克左右。 因此，在我的協議中，我個人只建議每晚補充60毫克-緩慢滴定。 研究表明，我們從這些水準的褪黑激素中獲得了我們想要的抗癌作用。 儘可能延長釋放時間，當你患上癌症時，最好避免使用所有B6補充劑，你可能會在褪黑激素補充劑中發現B6，如果它在你的補充劑中，你應該停止，你應該找到另一種補充劑。

一般建議在進行放射性成像掃描之前一次性進行更高的劑量，但請與您的綜合從業人員交談，瞭解如何在PET/CT掃描中用褪黑激素保護您的身體免受電離輻射的影響。

高劑量褪黑激素可能會有一些短期副作用，包括白天嗜睡、頭暈和頭痛。

褪黑激素可以與抗凝劑、抗靜劑和免疫調節藥物相互作用。 在將任何補充劑納入您的飲食計劃之前，請務必與您的從業人員交談。

具有最強支援訊號的癌症型別

乳腺癌

關於BRCA1突變雌激素陽性癌症的資料非常令人鼓舞。 「BRCA-1、p53、p21（WAF）和c-myc的表達被雌二醇上調。 用褪黑激素治療刺激細胞幾乎完全抵消了雌二醇引起的增加」這意味著雌激素導致乳腺癌細胞的生長和轉移潛力增加，有效地觸發了癌症過程。 將這些細胞暴露在褪黑激素中幾乎完全阻止了這個過程。

在一項研究中，褪黑激素抑制了乳腺癌細胞的入侵，降低了轉移的機率。

肺癌

那些在肺癌中癌症活性增加的人往往對褪黑激素受體的表達較低，而表達的增加會導致腫瘤生長緩慢。 「表達」的意思是，褪黑激素越高，跳入和佔據的機會就越多，阻斷補充褪黑激素的人肺癌的進展途徑。

肝癌（HCC）

發現對褪黑激素基因/受體（MTNR1B）敏感性降低的人患肝癌的風險更高。 （蘇等人，2017年）

褪黑激素和索拉芬尼的組合都減少了肝癌增殖基因AKT、CDK4/6和cMyc，這些基因與浸潤和轉移增加有關。

鱗狀細胞癌

在口服SCC中，還發現MT1受體越多，對褪黑激素抗癌作用的敏感性就越高。

最後一句話

褪黑激素不是一種神奇的治療方法，但它是綜合腫瘤學領域的有力競爭者。 它作為一種抗癌劑應該被認真對待，雖然我們還沒有進行人體試驗，但臨床前和當前的研究非常有希望。 我特別喜歡它支援健康的細胞，抑制癌症代謝，同時促進健康、安穩的睡眠，這對治療至關重要。