Rewrite of Niacin chapter

Statistics showed that the Niacin chapter of my book was the most read in recent times, but on a reread of it, I felt it needed a lot of work, so I put more time into it today, extending it to twice the size by writing about the interesting history of how Pellegra was eventually shown to be nutrition-caused and not infectious as was the common belief at the time.
Here is what I wrote:

Niacin and Pellagra

Niacin was discovered in 1837 by the Austrian chemist Hugo Weidel, who synthesised it by oxidising nicotine with nitric acid. He called the resulting compound "nicotinic acid". It was already known that a compound could be created by oxidising nicotine, but no-one had managed to create enough of the resulting acid to be able to figure out its properties.

Even though Niacin was discovered in 1837, it wasn't until 100 years later that it was recognised as a nutrient. The story for that leads through an epidemic in southern USA.


At the beginning of the twentieth century, in the southern US states, a large number of people started dying of a disease called "Black Tongue", "Zeism", or "Mal De La Rosa". We now call it pellegra. In 1914, it had escalated to the point that the United States senate declared it an epidemic and started working on figuring it out [1].

Symptoms included diarrhoea, mental confusion, loss of weight, weakness, irritation in the mouth and stomach linings, and lesions of the skin. Skin, especially that which was exposed to the sun, would become dark, thick, and scaly. The disease was sometimes misdiagnosed as leprosy. Sometimes the mental confusion would lead to depression, irrational violence, or lethargy.

Pellagra symptoms in the hands

Two our of every three people that exhibited signs of pellegra died of it.

It was believed, based on centuries of the disease in other countries, that pellegra was caused by diseased or spoiled corn.

The favoured meal of the day was corn-bread and mollasses. They were cheap and abundant. It was not easy then to get a varied diet.

North Carolina, for example, had a quarter of a million farms in the early 20th century, most of which were manned by low-waged people living on tenant-farms. The cash-crops at the time were cotton and tobacco. Food crops common at the time were wheat, oats, corn, rice, sweet potatoes [1]. If you wanted to eat, it would be made from those staples.

It was recognised by most doctors that pellegra was associated strongly with poverty and with diet.

However, the idea that people were dying because they were poor was politically distasteful, causing some politicians to utterly deny it. In Georgia, a senator was sent a wire stating "When this part of Georgia suffers from famine, the rest of the world will be dead!". Another group sent a letter to president Harding, said "Famine does not exist anywhere in the South, and we fail to find a general increase in pellagra". When people get stubborn, you can't show them what's right in front of them.

An alternative theory started to gain ground, that pellegra was an infectious disease, and therefore not related to poverty or diet. This theory had no evidence backing it, and existed purely because its proponents could not bear the shame that perhaps the USA was not feeding its workers properly.

Tests on prison inmates, orphans, and the insane

In 1914, Dr Joseph G Goldberger was assigned by the surgeon general to work on the problem, starting it by doing a three-week tour of a hospital, orphanages, and an asylum for the insane, which helped him confirm that Pellegra is not a communicable disease. Not one staff member at any of the institutions caught pellegra from the patients or inmates.

With an insight, Goldbeger noted the monotony of the meals that were provided at these institutions. He noted that even though patients and staff ate from the same menus, the staff usually ate first, taking the choicest meals and leaving the worst, and the staffcould supplement their meals with food bought elsewhere.

At the orphanages, pellegra did not occur in children under 6 or over 12. Goldbeger noted that the infants had meals supplemented with extra milk, and the older children were given work to do and then rewarded with better food.

The link was obvious, once pointed out. Goldbeger set out to prove it.

He set up an experiment using federal money, where some of the orphanages and some of the asylum inmates were fed with more varied diets. Everyone that was given the new varied diets recovered from their pellegra, and did not relapse.

He reported his success to the Public Health Service, but unfortunately had to stop the program when he ran out of funding. As soon as he did, the old diet was resumed in all places, and the patients started getting pellegra again.

The next year, in 1915, he presented his results at the Association for the Study of Pellegra. At the meetings, he was vilified by proponents of the infectious disease theory, and his cnclusion that a more varied diet was the solution, was ridiculed.

To prove his case, Dr Goldbeger decided he would cause pellegra. If he could selectively decide who got pellegra, and who didn't, and his decisions came true, that would be proof enough.

He got the help of a prison in Mississippi which had never had a case of pellegra, thus eliminating the "infectious" part of the argument. Eleven volunteer prisoners were housed separately from the rest and fed a strict diet of biscuits, gravy, grits (porridge made from corn), cornbread, rice, syrup (sugar), collards, and yams.

The experiment begane in February, and was stopped at the end of October. Pellegra was present in more than half of them. Goldberger was accused of torture. Even doctors who had applauded his efforts before were now criticising him. Skeptics were still not convinced pellegra was not infectious. You can't pleases everyone.

In another attempt to prove that pellegra was not infectious, Dr Goldbeger ran some "filth parties", where he injected himself, associates, and his wife with blood from infected pellegra patients, and ate dough balls which contained skin scales, urine, and faeces from pellegra sufferers. No-one contracted pellegra. There was some diarrhoeah and nausea, but that's understandable. The skeptics were again not convinced…

In the end, he stopped trying to convince people that refused to be convinced, and instead devoted his time to trying to find what was missing from the diets, based on the research he had done so far. He called it "PPF" (pellegra preventative factor). Others called it "vitamin G" (for Goldbeger).

His diet suggestions were noted, and saved many thousands of people, even before niacin was eventually isolated.

Goldbeger came across an animal insight. He became aware of a paper on malnutrition where doctors stufying malnutrition at Yale had fed dogs on a restricted diet of boiled peas, cracker meal, and cottonseed oil. The dogs developed symptoms that looked very much like pellegra, with sores and haemorrhages in the mouth leading it to have a blackened tongue.

Dogs in the south, around the area where pellegra was most active, had been noted to sometimes have a "canine plague" which the infectious theory proponents thought helped prove the idea that the disease was being carried from person to person, sometimes via dog.

One side effect of the ulcers in the mouth was that the dogs found it difficult to swallow. To help with this, owners sometimes used yeast as a salve, which helped cure the issues.

Goldbeger and his team realised that the yeast must contain the PPF.

In 1927, the Mississippi flooded, and Goldbeger was able to arrange for a large amount of the yeast to be shipped into places along the Mississippi that were afflicted. That year, the expected outbreaks of pellegra were dramatically reduced. Next year, however, the floods did not return, so he could not allocate the money again, and pellegra returned.

By now, it was well known (among those that would listen) that the cure was a varied diet, and the cause itself was a matter of narrowing down the possibilities.

The last thing that Goldbeger worked on before his death in 1929 was on trying to extract PPF from liver, which was found to be very effective in curing pellegra in both dogs and humans.

It wasn't until 1937, though, that the factor was eventually identified, and found by the biochemist Conrad Elvehjem, who had carried on the search.

PPF, the pellegra preventative factor, turned out to be nicotinic acid, now called niacin, which had been discovered 100 years before hand, but no use had been discovered for it.


It is now known that niacin treats pellegra, and can also be used to treat high blood cholesterol.

Very high doses can cause liver damage, but the damage will usually revert when if the level of niacin is brought down to the RDA. Overdosing at a 1-6g level can have a side-effect of lowering cholesterol, though, and this is used in treatment for hypercholesterolemia.

The recommended daily amounts for niacin are 16mg for males, and 14mg for females. 35mg will give you a "niacin flush", where the face or upper body turns red and feels like it is burning.

Parkinson’s Disease

Parkinson’s Disease (PD) affects the brain, making it difficult to coordinate movements. The ultimate cause is unknown, but the most obvious effect is that the brain produces less dopamine, and brain cells start to die.

While it is not directly fatal, the side-effects of PD (muscle rigidity, tremors, trouble swallowing, cognitive decline, increased chance of fatal falls, etc) make it more likely you will die early, raising the mortality ratio to twice that of the average person.

Currently, 1.8 deaths out of every 100,000 are PD-related.

It is commonly believed that there is no cure, with most efforts going towards treatment rather than an attempt to excise the disease. Initially, drugs such as Levodopa may be used. Where the drugs don’t work, deep-brain stimulation might be used instead. A recent breakthrough means that this might not require surgery.

Neural transplantation or cell replacement therapy (CRT) is an attempt to replace the neurons that have been lost to the disease, but the results on this method have been spotty up until now. There is a glimmer on the horizon, though – a recent paper showed it was possible to implant new healthy brain cells into affected brains, using an embedding matrix of cartilage to “ease” the implant, letting the new neurons integrate more securely.

CRT is the focus of a lot of research, with genetic modification being one of the avenues explored. A group called “GForce-PD” is working towards using CRISPR technology to correct dopamine production in neural grafts.

While we may not have a cure yet, I have no doubt it is on its way.

first human head transplant to be performed next month

I wrote about Sergio Canavero in my How To Live Forever book (online version here).

It’s just been announced that his long-awaited infamous operation, in which a living human head will be removed from a body and placed onto another, is to be performed next month in China. The location is not known. The patient is not known. The donor is not known.

If this fails, it will not be surprising, but it will also make it harder for any other experimental surgeons to get permission or patients to try again.

If it succeeds, then its fantastic and terrifying at the same time.

In a fantastic way, it means that people that have debilitating bodily conditions that cause weakness or paralysis have a chance to overcome all those issues at once.

In a terrifying way, it means that it science-fiction dystopian stories such as Spares or The Island step closer to reality – humans that are bred solely for the purpose of being a replacement body for an aging clone.

It is unlikely that “back-alley operations” will happen in this, as the expertise needed to do the surgery means that only the most educated and practiced ones could perform it, and that means that they could make easy money with legitimate operations instead, not needing to go underground to do it.

Is it possible to live forever with this method? A person with sufficient resources could use this trick to live for centuries, replacing their body every few decades. But, because age is about more than just the age of the body, this is just a way of prolonging life – the brain would eventually succumb to deterioration even if the body did not. In a way, it’s a way to live long enough to see proper immortality solutions to appear.

gene correction before transplant of new skin

Yesterday, the news broke of a series of operations performed on a young Syrian boy named Hassan who had a life-threatening disease, epidermolysis bullosa, which makes the skin liable to rip easily and tear away from the underlying layers because of its poor generation of laminin 332.

The boy had to have 80% of his epidermis (the outer layer of skin) completely removed and replaced.

His father had tried donating some of his own skin but the boy’s body rejected it, so scientists had to generate sheets of skin cloned from his own skin.

But there was no point doing that if the skin was just going to have the same problem, so they had to fix this problem.

The doctors contacted Michele De Luca of the University of Modena and Reggio Emilia’s Center for Regenerative Medicine, who had fixed a similar (but less severe) problem on someone’s legs before.

Michele extracted a sample of non-damaged skin from the boy, and subjected it to viral delivery system designed to replace the damaged LAMB3 gene in the skin’s DNA with a corrected copy.

After the virus had done its work, the skin was ready for growing. The scientists grew up to about a meter-squared of corrected skin before attaching it to the boy’s body in a short series of operations.

The operations were such as a success that there are no scars, only mild discolouration in some areas, and the kid can now run around like any other, playing rough games, getting battered and bruised, and most importantly, healing afterwards.

Most people seem impressed with the 80% skin replacement part of this story, but I think the most important part of it is that this was basically an instance of doctors taking a person’s own faulty organ, genetically correcting it, cloning a new one, and transplanting it back onto the body.

I believe this kind of trick can be used for many other disease types – not just skin diseases. For example, it is possible to 3D print new hearts using stem cells from your own body. If your heart is defective for genetic reasons, why not correct the issue before printing?

Lungs, veins and arteries. All of these can be 3D-printed. If yours are defective, it may be a choice soon to correct the defective genes, print new ones, and replace your defective parts.

We can rebuild you!

is it mathematically possible to live forever?

A story was released a few days ago saying that some scientists had proven with maths that it is impossible for halt aging.

Unfortunately, a lot of people are taking that at face value and think that it means that it is not possible to live forever. This is, fortunately, untrue.

It was “proven” in 2008 that humans couldn’t live past 125, and yet that was based purely on existing data and did not take into account our ability to solve issues.

The 125 limit is caused mostly by the Hayflick limit, which is a limit to how many times a somatic (normal – not stem) cell in the body can divide before its telomerase gets too short, telomerase being the bits at the end of the DNA that stop the DNA from being corrupted.

Of course, once humans identify a cause to a problem, we get out there and solve it. So, Elizabeth Parrish, an entrepreneur that runs the biotech company BioViva, became the first human to undertake telomere extension therapy, adding up to 18 years to her life.

The mathematical proof that was released a few days ago relies on the natural chaotic warring that happens between the various cells in the body from running itself ragged. But again – if we can spot a problem, we can solve it.

The research assumes that a living being, once born, will continue to live as-is until it simply dies of old age.

But we are hackers. We tinker. We see problems and fix them.

One of the issues is senescent cells (SnCs). We have already come up with a number of solutions to that which will be publically available within the next few years, including senolytics such as FOXO4-DRI and UBX0101.

I don’t accept that it is mathematically impossible to live forever. I believe these scientists have simply not considered all the variables.


I was just looking into where I could get some UBX0101 and came across a person on a forum saying that UBX0101 is Navitoclax, or is a derivative of it.

UBX0101 is a senolytic compound that was reported in July to be able to preemptively clear out osteoarthritis in healing wounds and cause lost cartilage to be regrown.

Navitoclax (also known as ABT-263) is a senolytic drug that has anti-cancer properties. It was evaluated in clinical trials in 2009 and approved in 2017 to work along with another drug, trametinib, to fight solid cancer tumours.

Navitoclax has a long-term side-effect that it can deplete levels of blood platelets, so it is not advised to make it a “one a day” tablet. If you take up to 150mg per day as well, it can cause vomiting, diarrhea, nausea. But I haven’t seen reports of any serious permanent side-effects.

It’s still quite expensive to buy – £267.75 for 100mg in one source. I wonder if there’s a cheaper source?

NMN treatment for Friedrich’s Ataxia

I was looking for updates on human trials for NMN (nicotinamide mononucleotide) when I noticed this.

NMN is one of a group of chemicals which is being looked at for their anti-senescence or senolytic properties. In NMN’s case, it helps to increase NAD+ in mitochondria, making it easier for older cells to generate energy to replicate correctly.

It turns out that NMN can also work with the SIRT3 protein to increase the presence of frataxin, which is a protein used in mitochondria and important for heart function.

People that have the disease Friedrich’s Ataxia have a mutation in their DNA which leads to reduced expression of frataxin in their mitochondria. Later in life, this leads to a list of issues, such as scoliosis, diabetes, heart disorders.

In mouse tests, it was shown that mice that had their frataxin-producing genes completely turned off were restored to good heart health after being treated with NMN.

cure for acute myeloid leukemia

In the 9th October edition of Cancer Cell, a paper was released which announced the first molecule that directly attacks just cancer cells (not healthy cells) and pushes them into apoptosis (cell suicide).

Titled “Direct Activation of BAX1 by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia“, the paper describes how the molecule, BTSA1, binds strongly to the activation sites on BAX, which is a protein in cells that triggers apoptosis, increasing the chance that the cell will be able to die properly.

You can think of this like a human messenger trying to send a message to someone (the damaged cell sending a message to itself to self-destruct), and a load of bullies constantly harassing the messenger, tripping her up and standing in her way (the cancer cell’s anti-apoptic proteins bind to the messenger protein). BTSA1 in this case is a strong security guard that travels with the messenger, pushing the bullies out of the way to let her send her message.

In normal cells, when it is time for a cell to die – for example, the telomeres are too short, or damage to the DNA is detected – messages are sent to the BAX protein to tell it to turn on cell suicide mode.

In some cancers, though, Acute Myeloid Leukemia (AML) in this instance, a number of “anti-apoptic” proteins are produced which bind to BAX, so it can’t send its message to start the apoptosis.

In this study, Evripidis Gavathiotis was able to find a molecule which binds stronger to BAX than the AML anti-apoptic proteins do, letting them do their job.

Most importantly, this increase in the strength of the BAX messages only affects those cells that are already trying to commit suicide (the cancer cells)- normal cells are left alone.

In mouse studies, some mice were given AML, and some of those then given the new molecule. Those that received the treatment survived weeks longer than those that did not, with 43% of the treated mice still alive three weeks after the control mice had died and no sign of AML in them.

Even though this treatment was specifically tested on just AML, it is possible that it affects other cancers as well. Dr Gavathiotis has been asked to repeat the test using other cancers to see if this is true.

Recently, the CAR-T cell therapy for cancer was announced which was able to kill cancer cells after some therapy such that a year later 64% of the patients were still in remission. With BTSA1, the chances look even better.

New chapter – good and bad habits

I recently read through a few hundred research papers to find references to “all cause mortality”, looking for studies done on various habits, in order to see what are the best habits to have in order to increase your lifespan.

I’ve converted the list into a chapter in my book (“How to Live Forever“) – a practical list of habits to take up or avoid. I think I did a good job of it!

The online version is here.

The items in the list are proven – I have links to the research papers right next to each point, and did my best to avoid any studies that had ridiculously low numbers in them (for example, a study of 5 people won’t get in the list, but there are a few where the cohort is larger than 100,000).

The list only contains common habits and practical tips. There is nothing in there about Quantum Immortality, for example, because that’s not a habit (and no-one really knows is quantum immortality real anyway). There’s also nothing in there about senolytics, because even though senolytics have a very profound ability to affect your lifespan, they’re not commonly available enough that you can make them into a habit.

Rewriting the Senescent Cells chapter

I rewrote the Senescent Cells chapter of my book (How to Live Forever), reducing the focus on FOXO4-DRI, and including details about alternatives such as UBX0101, Navitoclax and Quercetin.

The latter two have already passed human safety trials, but are designed primarily as cancer treatments. They do have senolytic properties, but those are not as strong as the actions that the FOXO4-DRI peptide and UBX0101 have.

The rewritten chapter is about twice as long as the original, but I think it’s written better. The original chapter is more terse and factual, while the new version is more conversational. It includes the same information (and more), but is much easier to read.

At the end of the chapter, I explained that even though the drugs themselves might be very expensive, the most important of them (in my opinion), can probably be synthesised at home, if you put some time and effort into it.

FOXO4-DRI is a patented drug, meaning that the creators wanted to protect who could sell it. In order to do this, they needed to describe it in full, which they did in the patent application. This included the protein sequence.

Patenting something is done to exclude others from selling or importing the patented device. Patents can also exclude people from making or using the device, but if there is no profit made, and the self-use of the device does no harm to the inventor’s business, it is extremely unlikely that any action would be taken. And even if action would be taken, it would be a mere “stop doing that” from the courts.

Personally, I’m firmly on the side of people creating and using what they create – especially if it involves saving your own life – so I’m building a workshop/lab in order to create drugs such as FOXO4-DRI for my own use.

So far, I have the frame of the lab built, and I’ve bought and calibrated a 3D printer for designing and building the lab equipment itself. I’ll probably write a second book explaining all that when I’m at a sufficiently advanced stage. I’ve just paid for the mechanical and chemical parts for a dehumidifier, which I’ll need to design because there are no 3D-printed desiccant-wheel dehumidifiers already in existence that I know of.

Anyway – next week, I’ll rewrite another chapter. The chapter on fixing DNA replication with NAD+ looks like it might be the next highest in popularity, so it gets a rewrite.