I decided to take advantage of my SARS-CoV-2 infected body and my putative biomarker of autophagy; the transient evening increased inflammation. First, I imbibed 2 tablespoons of Extra Virgin Olive Oil, which is about 65% oleic acid, half in the AM and half in the early PM. In the evening, from 6:30 till 10:30, I did notice increased inflammation via a headache. Not a terribly bad headache… but very noticeable. Hydroxytyrosol (HT) is a phenolic compound in olive oil that has antioxidant and anti‑inflammatory effects and enhances autophagy. Early research has revealed that HT can activate the silent information regulator 1 (SIRT1) pathway to induce autophagy.
https://www.spandidos-publications.com/10.3892/ijmm.2019.4300
The use of olive oil to induce autophagy is very interesting as it is cheap, safe and widely available. However not all olive oils are equal. The extra virgin, cold-pressed olive oils are thought to have the highest levels of Hydroxytyrosol. And the growing conditions before harvest may also influence the levels of hydroxytyrosol. Oleuropein is the compound found in Olive leaves and fruit that decomposes to hydroxytyrosol during processing or after consumption. Olive Leaf Extracts are normally 18 to 20% Oleuropein so represent a more standardized source of hydroxytyrosol. I have found that about 5mg of extract per pound of body weight is sufficient to induce autophagy for about 8 hrs in the late afternoon and evening.
I next tried Nicotinic Acid. To avoid the unpleasant flush reaction, I started with a lower dose and then increased it the next day. I started with 100 mg with breakfast and lunch, so a total of 200 mg. That evening… no change. The next day, I took 200 mg with breakfast and lunch, so a total of 400 mg. That evening, I had a nice headache and increased gut ache for 5-6 hrs. Induction of autophagy comparable to fasting. Vitamin B3 is found in two main forms in nature. Nicotinic Acid in plants and Niacinamide in animals.
https://link.springer.com/article/10.1007/s10522-020-09864-0
Niacinamide (aka Nicotinamide) has the advantages of being stable, water soluble, cheap and it does not trigger a flush reaction. I started with 1000 mg of Niacinamide and induced autophagy. Later I tried 500 mg of Niacinamide and that too nicely induced autophagy. Eventually, when trying out a daily low dose of Niacinamide, I found that even 200 mg could induce some authophagy in my time-restricted, low carb semi-fasting state. For a daily dose of niacinamide that DOES NOT trigger autophagy, I settled on 100 mg.
https://www.medchemexpress.com/Niacin.html
https://www.sciencedirect.com/science/article/abs/pii/S0271531716308181
Ketone Esters were up next. When a fasting body switches from burning glucose for fuel to burning fat for fuel, it is fatty acid ketones, in particular beta hydroxybutyrate, that are the main fuel source. Ketone Esters are known to induce autophagy in cell culture and are available as supplements – mainly to enhance long distance athletic performance in running and cycling. I took 5 ml of KetoneAid at mid-morning. To my surprise, the increased transient inflammation of my gut and brain began within 2 hrs. This method of inducing autophagy appears to not be coupled to the circadian clock in our cells. Anyway, I experienced a nice headache and gut ache for about 6 hrs. Again, strong induction of autophagy, at least as good as fasting. In the future I would use 4 or 5 ml of the KetoneAid Ke4 product.
https://pubmed.ncbi.nlm.nih.gov/15883160/
Powdered Coconut Oil was another autophagy experiment. Day 1 I took 10 g (1 scoop) at mid-morning. I did not feel any autophagy. Day 2 I took 30 g total 1 scoop mid-morning 2 scoops mid-afternoon. I felt a slight headache and a mental clarity beginning at 4:30 pm. By 5 pm I felt jittery or edgy. By 8 pm I had a gut ache. The autophagy continued till about 10:30 pm. For a total of 6 hrs. Coconut Oil powder is about half medium chain triglycerides or MCTs so I expect that MCT Oil would also be a potent inducer of autophagy. I rather liked the brain first emphasis I felt with Powdered Coconut Oil.
https://www.nature.com/articles/s41598-017-14376-y
https://pubmed.ncbi.nlm.nih.gov/26306884/
MCT Oil is a popular supplement, many people add 1 or 2 tablespoons to their bullet-proof coffee and grass-fed butter instead of eating breakfast. I took 1 Tbsp (14 g) with Matcha green tea at 6 am. I took another 1 Tbsp at 2 pm. Soon afterwards, 2:30 pm gut ache started and felt jittery like too much coffee. Feelings of autophagy basically till 9:30 pm. So about 7 hrs.
Last Fall, I tried Water for Life’s Hydrogen Water after a testimonial from a long-hauler that they fully recovered in 10 weeks by drinking 2 – 3 cans per day. Cautiously, I drank 1/2 can at 6 am. One hr later, I had a mild gut ache. It lasted a couple hours. At 12:15 pm I drank a full can. It induced autophagy an hour later and lasted several hours. To my surprise, at 7 pm in the evening, when NAD+ levels are rising, I again had a gut ache and headache for several hours. All in all, the H2 water was quite a good autophagy inducer. The H2 water along with the Ketone Esters were the first two compounds I found that bypass the circadian clock control of autophagy. Note, there are hydrogen pills available that allow you to more cheaply create your own hydrogen water.
https://www.hindawi.com/journals/bmri/2018/4670834/
I heard from other long-haulers that garlic cloves and onion tea can induce autophagy. I tried a tea consisting of 2 garlic cloves finely chopped and 1/2 white onion, coarsely chopped, steeped in hot water for 2 min. 1 hr later at noon I was feeling an increased headache and other symptoms of autophagy. Interesting that this is fast acting like Hydrogen water and Ketones. The feeling of autophagy lasted for about 5 hours. A good dose. Allicin is the bioactive compound in garlic that can induce autophagy and onions contain Quercitin.
https://pubmed.ncbi.nlm.nih.gov/22860996/
Omega 3 Fish Oil supplements also induces autophagy. I tried a 1250 mg fish oil concentrate with Omega 3 Fatty acids: 690 mg EPA and 260 mg DHA. It strongly induced autophagy. It also got rid of the brain fog I had been experiencing!
https://pubmed.ncbi.nlm.nih.gov/30409173/
Tumeric/Curcumin extract standardized to 95% curcuminoids 1200 mg. I took a 600 mg capsule with breakfast and another capsule for lunch for 2 consecutive days. The first evening I did not feel autophagy.. The second day from 2 pm until 11 pm I felt autophagy. What was unusual is that the transient inflammation did not happen all at once. Instead, it started with my gut, quite strongly for 3 hrs then as that tapered my right kidney was hit quite strongly for 3 hrs. Finally as that tapered, I got a mild headache for several hours. The inflammation was noticeable stronger for my gut and kidney compared to my head. The 24-34 hr delayed timing was unique also. Also noteable was that the autophagy feelings started at 2 pm rather than in the evening. Curcumin likely increases cellular ROS. A reference for Curcumin autophagy:
https://onlinelibrary.wiley.com/doi/10.1002/jcp.27404
Next I tested the idea that Ivermectin might be able to induce autophagy. I took the recommended dose of 0.2 mg/kg on day 1 and day 3 per the FLCCC I-Mask protocol. Ivermectin, failed to induce autophagy per my biomarker. It is thought that Ivermectin acts by blocking nuclear translocation of proteins… or other methods… but I had seen one report that it could induce autophagy in cell culture. After reviewing the research report, I realized that the researchers used a dose 20X higher than the 0.2 mg Ivermection/Kg that is the standard dose for humans. Update on Ivermectin I have heard from several other long-haulers that Ivermectin can trigger feelings of autophagy at 0.4 mg/kg and sometimes 0.2 mg/kg when taken daily. I am concerned that it could be inducing autophagy by causing ds DNA breaks causing SIRT1 to leave it’s normal binding site to repair the cellular DNA. Do we want to treat Covid-19 and Long Covid with a mutagen?
https://www.sciencedirect.com/science/article/abs/pii/S0045653520316428
Finally, I tried Metformin, a well characterized, cheap, widely available diabetes drug for 6 days. It induced autophagy at all the doses I tried, 300 mg, 500 mg, and 1000 mg. And like with the BHB ketone ester and the Hydrogen water the autophagy was not closely tied to the NAD+ regulated circadian rhythm. That is, I experienced my modest gut aches and slight headaches during the day an hour and a half after taking the Metformin… not just in the evening. This finding of autophagy induction is exciting because it potentially opens the door for medical doctors and GP’s worldwide to prescribe Metformin off-label for long covid!
https://www.sciencedirect.com/science/article/abs/pii/S1550413120301972
Trehalose is often mentioned in basic research on neurodegenerative diseases and induces autophagy. It is a unique sugar that allows the Resurrection Plant to survive almost full desiccation by stabilizing cell membranes. It is not part of people’s diets, but since the 90’s it has been used a substitute sweetener in some food products such as ice cream. I took 2 tsps (8-10g) on my oatmeal for breakfast. I had a mild headache within 2 hours. An hour later I had a gut ache plus the slight edgy/jittery feeling I associate with autophagy. My headache went away around 12:30 pm. But my gut ache continued until midnight. 15 – 16 hrs of autophagy. And this is a food that is considered GRAS – generally recognized as safe! In the future, 1 tsp would be a better dose.
https://pubmed.ncbi.nlm.nih.gov/30335591/
Manuka Honey is a special honey New Zealand where the Manuka bush is a native species. Manuka honey is renowed for it’s unique health benefits and it contains MGO – methylglyoxal a reactive glucose metabolite combines with certain protein residues to form damaging Advanced Glycation End products aka AGEs. Short-term treatment with MGO triggers autophagy. I tried Manuka Honey three times, once with 1.5 tsp of MGO 696+ honey (UMF 18), once with 1 Tbsp of MGO 696+ and once with 2 Tbsp of MGO 275+ honey (UMF 10). Each time I felt autophagy starting within 2 to 4 hrs. Interestingly, I also felt scattered joint pains in my wrist and ankle and a slight ringing in my ears. It kicked in during the evening, continued through the night and through the next morning. About 18 hrs of slow-burn autophagy. 1 Tbsp of MGO 696+ resulted in 22+ hrs of autophagy. The 2 Tbsp of MGO 275+ resulted in 7-8 hours of autophagy but then I had another wave of gut/organ inflammation the next day. There may be safer ways to induce autophagy as AGEs are damaging to a variety of cellular proteins and are associated with the health complicatios of diabetes. A good dose is 1 Tbsp of MGO 275+ or 1 tsp of MGO 696+.
https://www.sciencedirect.com/science/article/abs/pii/S0887233315001071?via%3Dihub
https://www.healthline.com/health/manuka-honey
Summary Initially, I thought it would be difficult to induce autophagy comparable to fasting. Amazingly, that is not the case. Based on my putative biomarker of 4-6 hrs of increased inflammation in the gut, the organ that I suspect is harboring a reservoir of SARS-CoV-2 virus, my confidence grows that my putative biomarker of autophagy is in fact a real autophagy biomarker. Thus, it appears very easy to perturb homeostatis in the cells of the body and to trigger autophagy though a wide variety of supplements and medicines.