The Vitamin–Liver Cancer Link I Didn’t Expect

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簡単な概要

このビデオでは、ビタミンKと肝臓がんの関係について解説しています。メタアナリシスや個別の臨床試験の結果を分析し、ビタミンKが肝臓がんの予防や治療にどのように影響するかを考察しています。主なポイントは以下の通りです。

  • ビタミンKは、細胞周期の停止や分化の誘導など、がん細胞の増殖を抑制するメカニズムを持つ可能性がある。
  • 複数の研究をまとめたメタアナリシスでは、ビタミンKの摂取が肝臓がんの再発リスクを低下させる可能性が示唆されている。
  • 最大規模の研究では、ビタミンKの予防効果は確認されなかったが、既存の肝臓がんの治療においては有望な結果も存在する。

導入

ビタミンKに関する一般的な話題は心血管疾患との関連ですが、最近のメタアナリシスでは、ビタミンKの摂取が肝臓がんに及ぼす影響に注目が集まっています。このビデオでは、メタアナリシスだけでなく、関連する個別の臨床試験の結果も詳細に分析し、ビタミンKと肝臓がんの関係について解説します。

ビタミンKと肝臓がん:その理由

ビタミンKが肝臓がんに対して有益である可能性が示唆されるメカニズムは複数存在します。その中でも重要なのは、細胞周期の停止と分化の誘導です。細胞周期の停止とは、がん細胞の分裂を抑制する効果を指します。ビタミンKは、細胞周期の進行に必要なタンパク質であるサイクリンD1の生成を抑制することで、がん細胞の分裂を抑制すると考えられています。また、ビタミンKは、がん細胞に分化を促す作用もあります。がん細胞は未分化な状態を保ち、無限に分裂を繰り返しますが、ビタミンKはがん細胞に特定の役割を与え、分化させることで、その異常な増殖を抑制すると考えられています。

11件の研究:肯定と否定

11件の研究をまとめたメタアナリシスの結果、ビタミンKの摂取が肝臓がんのリスクを低下させる可能性が示唆されました。メタアナリシスでは、研究参加者の肝臓がん発症からの期間(1年、2年、3年)ごとにデータを分析し、ビタミンKを摂取したグループとそうでないグループを比較しています。その結果、全体として、ビタミンKを摂取したグループの方が肝臓がんの発症リスクが低いことが示されました。ただし、メタアナリシスには、無作為化比較試験と観察研究が混在しているという弱点があります。無作為化比較試験の方が厳密な管理が行われているため、観察研究の影響は比較的小さいと考えられます。

最大規模の研究の反論

メタアナリシスに含まれる最大規模の研究である吉田らの研究では、ビタミンKの摂取による肝臓がんへの効果は確認されませんでした。この研究では、疾患のない生存期間を指標として、ビタミンKを摂取したグループとそうでないグループを比較しましたが、両グループ間に有意な差は見られませんでした。同様の結果を示す研究も複数存在します。この理由として、研究期間の短さや対象者の特性などが考えられますが、最も重要なのは、研究の目的が肝臓がんの再発予防であったことです。

肝臓がん患者への適用

メタアナリシスでは、肝臓がんの治療後の再発予防に焦点が当てられていましたが、既存の肝臓がんに対するビタミンKの効果を示す研究も存在します。これらの研究では、肝臓がんの治療に加えてビタミンKを投与したグループと、治療のみを行ったグループを比較し、がんの進行度合いを評価しています。その結果、ビタミンKを投与したグループの方が、がんの進行が抑制される傾向が見られました。したがって、ビタミンKは、肝臓がんの治療と併用することで、より効果を発揮する可能性があると考えられます。

肝臓がん未経験者への適用

肝臓がんの経験がない人が、将来的な肝臓がんの予防のためにビタミンKを摂取することの有効性については、まだ十分なエビデンスがありません。単一の研究では、肝疾患を持つ女性を対象に、ビタミンKの摂取が肝臓がんの発症リスクを低下させる可能性が示唆されていますが、サンプルサイズが小さく、対象者が肝疾患を持つ女性に限定されているため、結果を一般化することはできません。したがって、現時点では、肝臓がんの予防に対するビタミンKの効果については、さらなる研究が必要です。研究で使用されたビタミンKの一般的な形態はビタミンK2であり、投与量は1日あたり30mgから90mgの範囲でした。

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0:00 The typical talk in relation to vitamin K is its relationship to cardiovascular disease. But the reality is that there's a new metaanalysis of 11 mostly randomized control trials that caught me by surprise because it looks at what happens when people supplement with vitamin K and we test cancer, specifically liver cancer. As usual, I not only went through the meta analysis, but I opened up as many individual randomized control trials as I could get my hands on. That's eight additional studies. And as usual, there's disagreement, especially in the biggest randomized control trial. But have no fear. I have answers and clarity that shall shine through like a ray of sunshine through clouds in the heavens.

0:48 Okay, before I jump into the data, you may be wondering like I was exactly how vitamin K is proposed to offer this benefit. I mean, it's a vitamin, okay, but what exactly is it doing? Now, there's a bunch of proposed mechanisms, like I'm talking like eight or more. So, we aren't going to go over all of them. Happy to cover that in future analyses for you. But some of the cooler ones are the initiation of cell cycle arrest. So, when your cells divide, same with cancer cells, they undergo cell division, the literal copying and appropriate division of components of the cell to form a new cell. This whole process is driven by something called the cell cycle meaning different signals that have to come together and report in yes ready to divide during the initial phase called

1:36 G1. It's this checklist that vitamin K is believed to inhibit because one protein called cycl D1 which is critical for this checklist is produced less meaning that the cancer cell has less signaling telling it to divide. A key feature of cancer. Another described mechanism is that vitamin K can force something called differentiation. Now one of the key issues with cancer is that they remain partially undifferentiated. That means that they do not have the identity like a muscle cell or a brain cell or a liver cell and so on. So they are able to divide constantly because they're not programmed to stop dividing like many other cells. But vitamin K essentially slaps them on the wrist and forces them

2:22 to differentiate, which means that they receive an identity, a job, stopping them from their hooligan ways of constantly dividing for no reason other than to cause havoc. Damn teenagers. That's two in a broad sense. Like I said, much more to explore here. And if this video does well, I'm happy to delve into the nerdy details and discuss the various ways vitamin K is supposed to protect against cancer and combat cancer. For now, let's just say that vitamin K makes it more difficult for cancer cells to divide. Now, when we put 11 studies together like the researchers of this meta analysis did, we get results like these. I know it looks like a lot, but it's actually pretty easy to understand. There's three graphs because the researchers separated the data by how long people were liver cancer free

3:10 over one year, two years or three years. Now you can see the studies on the left side and the data extracted from each study in the middle. But importantly to you are the visual results on the right side. So each box represents the comparison of vitamin K supplementation to the control group. So the nonvitamin K. If the boxes move to the left, that means that there's reduced risk of developing liver cancer. Even easier is to look at the overall results, all the studies combined shown on the black diamond in each graph. And clearly by the black diamond, there's reduced risk of developing liver cancer if people supplemented with vitamin K. One thing that annoys me about some meta analyses is the weaknesses in design, though. For example, this analysis mixes randomized control trials with associative studies.

3:57 This can be an issue because randomized control trials are more rigorously controlled for influencing factors on the results and associative studies are well to put simply not. Fortunately, the majority of the included studies were controlled trials. So the influence of these less controlled studies is likely pretty small. There are still other gripes that I have, but that's the biggest one. still saving you from my complaints. We can say that this analysis indicates a reduced risk of liver cancer recurrence from vitamin K consumption. Notice how I said recurrence, meaning people who already had liver cancer or had significant liver disease of some sort. That's important, especially as I turn your attention to the biggest study. Notice this one included in the analysis, the Yoshida study has a big square because

4:45 it's a big study, which means it has a lot of weight. I mean a lot of influence yet you'll notice that it sits firmly in the middle line indicating in no uncertain terms that vitamin K does not have a benefit when consumed. So why is that? Fortunately this is one of the studies I could get my hands on. And sure enough there's no doubt as seen here we're looking at disease-free survival. So the higher the lines remain the better. You can see that the three lines, tough to tease out, but it doesn't really matter because the black line, the non-vitamin K supplemented, is not much different from both vitamin K supplemented groups, meaning that there's no benefit of vitamin K, confirming that big square in the meta analysis. This result is not isolated.

5:32 In fact, several other studies show the same result. No effect of vitamin K supplementation. There are a number of possibilities from the fact that some studies were shorter in duration and you're measuring a long acting disease like cancer to the people tested considering that most studies were quite small. But the most consistent explanation that I found is the outcome itself. Remember the word recurrence. That means that people had cancer treated or surgically removed the liver cancer and then were placed on vitamin K as a preventative. However, if we look at other outcomes like people who still have liver cancer, which was not included in the meta analysis as it focused on recovery from cancer, there are some encouraging results here. The participants were given the cancer treatment, which is the blue line, or

6:18 the cancer treatment plus vitamin K, the green line. We're measuring the progression of already existent liver cancer. The lower the lines go, the worse. Clearly, the vitamin K had a noticeable effect. And again, this is confirmed in other studies. So based on this dividing feature, the outcome, we could tentatively say that vitamin K used as a preventative for future liver cancer after liver cancer treatment has mixed evidence and a lot of uncertainty. However, when a person currently has liver cancer and is treating that liver cancer with medicine plus vitamin K, there's better evidence that vitamin K is effective. This leaves us with two outstanding questions, though. One, you may be watching this thinking, "Well, dude, I don't have or nor have I ever

7:07 had liver cancer, so would it be effective for me? And two, bro, quit playing with me. What's the dose? What's the type of vitamin K? Tell it to me straight." All right. All right. We'll discuss those next and quickly. But if you're interested in learning how vitamin K may be more effective for some people based on particular features or how vitamin K affects something called DCP, which is related to liver cancer, or the impact of vitamin K on overall mortality risk, then check out my full analysis. It's included as a physionic insider. What do we have for them, Janine? That's right. a library of a hundred plus ad free videos, accompanying articles, one paragraph summaries for every single

7:54 video, live sessions with me, and what's that? Huh? A private podcast access and more. Well, Janine, sounds like the Physionic Insiders is the place to be to join. Where do they need to go? Ah, yes, of course. Well, you heard it there, folks. The description box of the video naturally. Thank you, Janine. There is a single study that's been done in people without liver cancer and when measuring how likely it is to develop initial liver cancer. The higher the lines go, the worse as more people develop liver cancer over several years. Clearly, the vitamin K supplementing group had lower risk. I should point out though, this was a small study only including women and was limited to women with liver

8:39 disease like cerosis. So, while not liver cancer, they weren't in great shape to start. So the results may be different when testing people with healthier livers over time and looking at spontaneous cancer. So we should frame this as uh we have early human evidence that vitamin K may be protective against developing initial liver cancer. Now across every study the most common form of vitamin K was vitamin K2 and the doses ranged from the bottom end of 30 milligs up to 90 milligrams total daily consumption. Usually vitamin K was consumed two or three times throughout the day in capsule form. Also keep in mind that these studies are small. So the ability to really assess safety is always

9:24 dampened. And there can be some interactions between vitamin K and certain medications. So don't jump in without a good think and maybe I don't know a discussion with your physician. And talking about vitamin K, I have more on its effects right here. Or if you prefer more on ways of reducing cancer risk, then check this out right here. As always, I deeply appreciate you swinging by. I hope to get to speak to your stone solid, unsmiling face again in the next video. What was that? A smile I saw. No, must have been a flicker of the light. I'll catch you in the next one. Bye.

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