Fasting and Fisetin

As far as I understand it fasting has a multitude of benefits beyond just losing weight. You have autophagy and apoptosis, an increase in growth hormone, a reduction in insulin resistance, a reduction through the loss of fat in production of oestrogen and much else besides on the cellular level. You’re also reducing or getting rid of that damaging visceral fat. In fact, many new drugs being developed for dealing with what has been dubbed ‘metabolic syndrome’, i.e. poor lifestyle choices, have effects that are the same as those fasting produces. Psychologically you’re taking control of your body and that, though I hate the word, is empowering.

Combine fasting with exercise and the benefits ramp up. I’ve been fasting now for nigh on two months spending two days a week without food. Also, throughout this time, I’ve been walking longish distances at the weekends and hitting the gym for 50mins three to four times every week. I’m steadily closing on having lost 20lbs of fat, feel light and have better muscle definition, and am feeling pretty good about that. But, as ever, I have to go one step further.

My weight loss has been steadily declining. At the start of this fasting period I was losing (if you discount the large water loss) getting on for 3lbs a week. It’s now down to about half that. I know from my reading that the longer you fast the longer you spend in ketosis and autophagy so the greater benefits you get from them. Because Julie was going away this last weekend I decided to go for a four-day fast and see how I got on with that.

Other reading added something else too. I know that to retard the effects of aging and for good health, weight loss (best through fasting) and exercise are two of the things we as individuals can do. But now another looms on the horizon. A lot, if not most, of the damage of aging comes from senescent cells. These are cells that have malfunctioned but, due to the nature of that malfunction, have not been destroyed by the body. They sit inside us producing SASP – Senescent-Associated Secretory Phenotype – which causes inflammation and has been linked to many disorders. Now studies have shown that by using a senolytic – a drug that causes apoptosis (death) of these malfunctioning cells – one can to a degree reverse some of the effects of aging.

Few senolytics are available. The most effective (in mouse studies) has been a combination of a cancer drug called dasatinib and an over-the-counter supplement called quercetin. The quercetin doesn’t do very much by itself. But there are others that are easily available to us. One is in long pepper – a substance called piperlongumin. Another is fisetin – the flavonoid that gives strawberries their colour. Apparently this last may be best of all and can work without a toxic cancer drug involved. So I decided to use some.

Apparently just a few fisetin capsules don’t have the required senolytic effect. You need to megadose with it, but this stuff supposedly has nothing in the way of adverse side effects. My searches and calculations gave me a dosage of 640mg of pure fisetin (the capsules you buy will have a percentage of fisetin) per day for five days. It is also lipophilic so taking it with an oil of some kind will promote absorption. I raised the dosage to 1000mg a day since I was doing it for four days and not five. The first two days I emptied the capsules into MCT oil and drank it. The stuff tasted foul and after the first two days I could not face it like that so took it in capsule form with fish oil and an MCT/coconut oil coffee on top. That was better.

Now, on the day following all of this, I don’t yet know what effects it has had beyond the immediate effects of the fast itself. The fisetin might not have been sufficiently bioavailable taken by mouth. It might also be the case, as with exercise, that the best results only show up properly after rest and food. Of course I may see nothing at all. Killing off senescent cells does not turn one into superman, but returns one to a previous normal – while the effects of aging are very gradual indeed.

6 thoughts on “Fasting and Fisetin

  1. Nice post… good to hear people experimenting with alternative methods to delay ageing!

    What brand of fisetin did you go for?

  2. I would like to purchase a hard cover version of The Line of Polity and donate it to my local library as it is the one book they do not have if your series. I can only find paper back. Can you tell me to find a hard cover? Sorry if this is a silly question. I enjoy your books, please keep writing. I saw no other way to contact you then leaving this post. Tony

  3. HI Neal

    Hello from New Zealand.

    I ran with the 5 : 2 for a while and lost a lot of weight. More recently, in response to the work of Valter Longo, I tried 5 X four day fasts (with exercise) over about six months. Longo’s research, (solid, peer reviewed, published) supports what you say above about the autophagy and apoptosis but also he discovered that the metabolically compromised cells that are sacrificed during the fast are replaced by stem cells once you re-feed: at least in the case of white blood cells which is what he measured. Longo speculates that the same process may be occurring in a number of tissue types and organs. This means that you can not only remove senescent cells but replace them with new cells = rejuvenation.

    I also have been looking into Senolytics. My interest in Fisetin is based on this recent article published in Lancet. It is incredibly thorough research, they even look into translatability to human tissue.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/

    They used 60mg per kg (oral) for about eight days twice in the mouse lifespan. The results are incredible. That translates linearly to a lot of Fisetin for a human though. The standard approach to scale up to early stage human safety trials is outlined in this paper.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/

    It basically comes out to about 20mg/kg for five days as a safe level trial for initial human trials. I took 1000mg of Fisetin for four days recently.

    They tested a number of potential candidates in the paper above. Curcumin also came out reasonably well in terms of readily available supplements. I also take Circumin but not in mega doses, although I intend to along with Piperlongumine.

    WRT human trials there have been very few on any of these. Most has been done on the dasatinib quercetin combination but the former is an ugly and expensive drug. On naturally occurring Senolytics we are out on our own in the land of the unknown Neal.

    The Mayo Clinic ran a trial on aged women for two days recently with some good empirical results on walking and other mobility measurements but no measured results on the target disease (Fibrosis).

    Anyway I’m going to do another Fisetin “trial” at a higher does in a few weeks.

    I feel great as a result of all of this but it could all be due to placebo, weight loss and exercise. Anyway my point is that all of what you are doing is based on strong research not internet flackery. Good luck with it.

    Finally, Neal I have just finished my first SF novel. If you have any advice on getting published I would love to hear it. Kind regards Ross Mitchell

  4. I’ve megadosed with DMSO and choline to help iptake. It’s a dopamine agonist, so be careful if you have plans because the sleep thing. Took like 8 grams.

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