甲福明安全吗？甲福明（降糖药）衰老临床试验的剂量是每天1700毫克。下图的老鼠研究剂量是300和100毫克/公斤/天。假设平均60公斤的人，大约28毫克/公斤。这大约是老鼠剂量的十分之一到三分之一。

Is metformin safe? The dose for the metformin aging clinical trial is 1700 mg per day. The mouse study doses from the graphs below are 300 and 100 mg/kg/day. Assuming an average 60 kg person, that's about 28 mg/kg. This is about one-third to one-tenth the dose that mice got. 

对人类来说，这是一个相当严厉的剂量，但还是在指导剂量限值内，所以危险的副作用的风险还是很低的。在相似的剂量率下，甲福明诱发乳酸血症病例机率为3人/100000例患者年。乳酸酸中毒致死率为1.5人/100000例患者年。对于这一临床试验，不应该有问题。但是如果推出至第四阶段（FDA批准），我们应该预期一些人会死于过度接受这种药物。该流行病学的确定性值得让甲福明被容易获得吗？我想是的。这大概是跑马拉松的人的死亡率的两倍。（奇怪的是，几乎所有人死于最后一英里）。略低于1.77人/100000人游泳时死亡的风险。

For humans, it's a fairly stiff dose, but well inside guidelines, so risk of dangerous side effects is low. Metformin induced lactic acidosis cases have been 3 per 100,000 patient years at similar dose rates. Fatality from lactic acidosis has been 1.5 per 100,000 patient years. For this clinical trial, there shouldn't be problems. But if rolled out to stage 4 (FDA approval) we should expect a few people to die from over-enthusiastic embrace of this drug. Is that epidemiological certainty worth making metformin easily available? I think so. That is about double the death rate for people running marathons. (Curiously, almost all of them die in the last mile.) It's a bit lower than the 1.77 per 100,000 risk of death while swimming.

甲福明的一个令人不安的问题，因为它踢出了一个生成类淀粉蛋白的途径,。一些迹象表明，使用甲福明的2型糖尿病患者比那些不使用的认知功能差。其他有人认为它可能防止阿尔茨海默氏症，但这是一种投机。

There is one disquieting concern with metformin because it kicks up a pathway that produces amyloid. And some indications are that type 2 diabetics using metformin have poorer cognition than those who don't. Others suggest it might prevent Alzheimer's, but that is speculation.

甲福明会让人活到100岁吗？这里有多个对鼠类的研究，比较了各种药物和环境干预措施。这种药物作用结果的外缘是寿命增加了20%。甲福明作用的结果从2.27%到20.71%不等，对小鼠的施药是从生命极早期开始的。平均寿命延长6.87%，这是正好介于高热食品？和伽马射线辐照之间。

Is metformin going to get people to 100 years of age? Here are multiple studies from rats and mice comparing various drugs and environmental interventions. A 20% increase in life span is the outside edge of results for this drug. Metformin results range from 2.27% up to 20.71%, and treated mice from fairly early in life. The median life span extension is 6.87%, which is right between cage enrichment and gamma ray irradiation.

大多数人在晚年会服用甲福明。所以希望人们活过120%的正常寿命（额外的14年左右）是非常不可能的。没有理由期望一个明显可观测到的效果。如果有，那么它应该在较低的个位数。如果你是一个男人，你可能会看到最多多活2至3年。如果你是一个女人，也许是4年。

Most people will start taking metformin late. So expecting people to live 120% of normal life span (an extra 14 years or so) is very unlikely. There is little reason to expect a large observable effect. If there is, then it should be in the low single digits. If you are a man, you might see at most 2-3 years more. If you are a woman, perhaps 4.

甲福明如何与其它可选项抗衡？How does metformin stack up against alternatives?

伽马射线照射的小鼠寿命延长了6.5%，这是如此接近甲福明的中值。我喜欢用γ辐照作为基准，它比较引人注目。这些动物在0.07 cGy/h（厘戈瑞/小时）的持续辐照下，直到他们得到一个4.5Gy的累积剂量。（他们无法对小鼠辐照更多的剂量，因为他们没有活足够长的时间。那是连续267天，24 x7的伽马辐射）。如果地球上的某个建筑物正好有那样的辐射水平，它会有迹象。这是一个6.132西弗特的年剂量。(伽马射线与西弗特一一对应，生物效应的测量，所以这里的数字是相同的)。给你一个多少的概念，这是切尔诺贝利那次事故后第一年内部疏散区的14倍，是NRC核工人每年上限的122倍。

Gamma ray irradiation extended mouse life span by 6.5%, which is so close to the median for metformin it hardly matters. I like to use gamma irradiation as a benchmark – it gets a person's attention. These animals were dosed at 0.07 centigray per hour continuously, until they got a dose of 4.5 gray. (They couldn't dose the mice more than that because they didn't live long enough. That's 267 days of continuous, 24x7 gamma radiation.) If some building on earth had that level of radiation, there would be signs all over it. That is a yearly dose of 6.132 Sievert. (Gamma rays have a one-to-one correspondence with Sieverts, the measure of biological effect, so the numbers are the same here.) To give you a sense for how much that is, it is 14 times the inner evacuation zone at Chernobyl, in the first year after that accident. It is 122 times the NRC nuclear worker limit per year.

这是一个特殊的鼠系，AKR / J，得白血病/淋巴瘤的机率约为90%。所以，认为辐射治疗帮助了病鼠，但是一般来说，这些老鼠之所以被选择，是因为他们更容易生病，而不是更少生病，当暴露于致癌物时。还有来自台湾的2006年的一篇论文显示，住在伽马射线辐照水平两倍于NRC的核工人50 mSv的极限的公寓里的人们的非常低的癌症发病率。因为人一生中患癌症的风险是，男性是2个中有1个，女性是3个中有1个。,如果连续辐照大大削减了癌症发病率，这应该转化为寿命的显著提高。

This is a special mouse strain, AKR/J, which gets leukemia/lymphoma at about a 90% rate. So, it could be argued that the sick mice were helped by radiation treatments, but generally, these kinds of mice are chosen because they get sick more easily, not less, when exposed to carcinogens. There is also a 2006 paper from Taiwan that showed radically lower cancer incidence in people who lived in apartments that irradiated them with gamma rays at levels up to nearly double the NRC's nuclear worker limit of 50 mSv. Since the overall lifetime risk of getting cancer is about 1 in 2 for men and 1 in 3 for women, if continuous irradiation cuts cancer rate dramatically, that should translate into a significant gain in life span.

巧克力可能有类似于甲福明的总体效果。Acticoa，一个瑞士产品，改善认知功能并增加寿命达11%。类似于甲福明，这个巧克力产品显示了一些癌症预防活性。所以你可能从某些巧克力制品中获得类似于甲福明的结果。

Chocolate may have as large an overall effect as metformin. Acticoa, a Swiss product, improved cognition and increased life span by 11%. Similarly to metformin, this chocolate product shows some cancer prevention activity. So you can probably get similar results from the right chocolate preparation as from metformin.

哪个更好？这是真的很难说。甲福明是可以一试的好东西。这是一个FDA以前从未审查过的新的族中的新的治疗种类的第一步，这很好，但它不是城里唯一的游戏，绝对没有希望。

Which is better? That's really hard to say. Metformin is a good thing to try. It's a foot in the door for a new class of treatments in a new category the FDA has never reviewed before, and that's good. But it's not the only game in town, not by a long shot.