How To Induce Autophagy Without Fasting [Updated 2024]

Q: What is spermidine?

Spermidine is a powerful polyamine that promotes autophagy , the body’s cellular “clean-up” process, and inhibits 9 of the 12 scientifically identified root causes of aging, known as the “Hallmarks of Aging.” While two-thirds of the body’s spermidine is produced by the gut and body tissues, the remaining third comes from food. As we age, natural spermidine production declines, so maintaining youthful levels requires external sources, either from spermidine-rich foods or supplements like Primeadine.

May 21, 2021

By Leslie Kenny

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Woman performing rigorous exercise | Oxford Healthspan

Autophagy & Fasting

Fasting triggers our body's ability to clean and renew its own cells, known as autophagy.

But the problem is that fasting isn't so easy for everyone. And new research [1] indicates it might not be as healthy as we once thought either.

As someone with hypothyroidism, I have never found fasting easy. Fasting with hypothyroidism causes our bodies to think we are going into a sustained period of starvation, and in its wisdom tries to protect our ability to survive by down regulating our metabolism and making it difficult for bioavailable T3, one of our key thryoid hormones, from attaching to the receptors in our cells. At the same time, our bodies adrenal glands will increase cortisol production as a way to better regulate blood sugar, but this can lead to chronic inflammation and decreased production of melatonin. If that weren't bad enough, all that extra cortisol has to be made from another key hormone, progesterone, which helps us sleep, but also helps balance out our estrogen levels.

I think you can see why some of us would be highly motivated to find ways to trigger autophagy without having to fast!

How to Trigger Autophagy

Autophagy Supplements & Foods

Have you heard of spermidine? Spermidine is a natural polyamine we produce in our gut biomes that, just like our body's autophagy process, reduces as we age. Thankfully, we can get it from spermidine-rich foods like Japanese fermented natto, tempeh, mature cheddar cheese, and food-derived spermidine supplements.

Spermidine has been proven to induce autophagy [2] and acts as a calorie restriction mimetic, providing all the benefits of fasting without the pain. It also inhibits 9 of the 12 hallmarks of aging (the pathways through which your body ages and what is responsible for the signs and symptoms of aging) [3].

Our premium, food-derived spermidine supplement, Primeadine, is made from food-derived concentrated wheat germ and offers a highly bioavailable way to up your spermidine intake. It's rigorously tested for purity and potency in Japan and the USA and some of the benefits of triggering autophagy and inhibiting the hallmarks of aging that you can expect include:

Improved hair growth, quality and thickness (including lashes and eyebrows)
Healthier nails and skin
Better, deeper sleep
Improved cognition and reduced brain fog
Feeling more vibrant and vital

And of course, all of the benefits you can't see and feel but are happening as a result of kickstarting your cellular renewal process.

Learn more about our autophagy-inducing supplement, Primeadine, here.

Autophagy & The Keto Diet

By going on a ketogenic diet where 75% of our caloric intake comes from healthy fats and 5-10% comes from carbs is a great way to trigger autophagy [4].

Examples of healthy fats would be Extra Virgin Olive Oil (EVOO), grass-fed ghee, grass-fed butter, Medium Chain Trigylcerides (MCT's) including caprylic acid, or C8. The fats keep you sated, but importantly they provide ketones which can service over 70% of the brain's energy requirements.

And for those of you who think going keto is going to be really hard, well, I've got news for you: you have already been in ketosis and you never even noticed it!

What am I talking about?

We are all *born* in ketosis. That's right. When we are in our mother's wombs we are in ketosis. And we continue to remain in ketosis when we are breastfed by our mothers.

There have even been studies showing that the ketone receptors in the brains of Alzheimer's patients are still fully functional, whereas the gylcogen receptors don't seem to work as well and are even covered by a biofilm preventing gylcogen from attaching to its receptor and getting into the brain cells.

I hope I've made it clear that healthy fats are good for you. And olive oil and fish oils are my top choices.

I personally also love grass-fed ghee, which does not have either the lactose nor the casein proteins (A1 and A2) that many can be allergic to. However, for those of you who have done your 23andme.com tests and know you have 1 or 2 of the APOE4 genes, you will need to avoid saturated fat due to increased risk for neurodegenerative issues. Olive oil and fish oil by contrast will help you.

You can find more inspiration by going to visit our friends over at KetoDiet blog for recipes and information (no affiliation, just friends!).

Exercise-induced Autophagy

Another way you can trigger autophagy without fasting is through intense exercise [5, 6, 7]. I'm not talking about running a marathon. As a matter of fact, you can do some pretty time efficient exercise by using weights for resistance training incorporated into your circuit training.

Again, I feel the Japanese have really got this one nailed with the Ka'atsu device, which uses Blood Flow Restriction and Moderation to build muscle, increase growth hormone and nitric oxide in as short a time as possible. There are beauty benefits from this as well with Japanese aestheticians incorporating this into their spa offerings to enhance blood flow to skin, hair and nails.

You can check this out by going to the lovely folks at Ka'atsu Global or visiting their Ka'atsu YouTube channel. You can get 15% off with the code OXFORD15.

Another great hack you can use is Dr John Jaquish's X3 Bar which allows you to use both your own body weight and some extremely strong, durable and (even for the strongest of you) challenging resistance bands. These are hooked to a unique metal bar which moves such that you can't put too much strain on the weakest load-bearing link, in this case, your wrists.

Most OsteoStrong bone building clinics in the US also carry them for use on-site as they are great for building muscle but you should also be able to purchase them there as well.

Autophagy & Sleep

Sleep is another great way to induce autophagy. It has been shown that when we get fragmented sleep, we stop the body's ability to induce autophagy [8]. Uninterrupted sleep is another challenge as we get older and underscores the importance of taking the time to exercise which has been shown to positively influence sleep, wind down properly away from blue-light emitting devices which keep our cortisol levels up while suppressing production of the sleep hormone melatonin and using up stores of progesterone which also help us sleep.

In addition to the fact spermidine triggers autophagy, it has also been shown to modulate 2 of the 8 clock genes that regulate the circadian rhythm. As a result, our clients have reported increased Deep Sleep, as seen on their wearable sleep tracking devices. Kill two birds with one stone and supplement with our food-derived spermidine supplements, Primeadine. Learn more here.

References

1. 8-hour time-restricted eating linked to a 91% higher risk of cardiovascular death
https://www.sciencedaily.com/releases/2024/03/240320115727.htm

2. Madeo F, Bauer MA, Carmona-Gutierrez D, Kroemer G. Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans? Autophagy. 2019 Jan;15(1):165-168. doi: 10.1080/15548627.2018.1530929. Epub 2018 Oct 11. PMID: 30306826; PMCID: PMC6287690.

3. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3. PMID: 36599349.

4. Emerging Role of Mammalian Autophagy in Ketogenesis to Overcome Starvation: https://www.ncbi.nlm.nih.gov/pubmed/27050461

5. Exercise and Exercise Training-Induce Increase in Autophagy Markers in Human Skeletal Muscle: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889490/

6. Exercise Induces Autophagy In Peripheral Tissues and In The Brain: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463459/

7. Exercise-Induced BCL2-Regulated Autophagy Is Required For Muscle Glucose Homeostasis: https://www.ncbi.nlm.nih.gov/pubmed/22258505

8. Circadian Rhythm of Autophagy Proteins in Hippocampus Is Blunted By Sleep Fragmentation: https://www.ncbi.nlm.nih.gov/pubmed/27078501

Leslie Kenny, MBA (Harvard), BA East Asian Studies (Berkeley), Dip. Health Coach (IIN)

Leslie Kenny is an Oxford-based entrepreneur from Southern California and a graduate of Berkeley and Harvard Business School. In her 30s, her life changed dramatically when she was diagnosed with an array of autoimmune conditions - lupus, rheumatoid arthritis, and hypothyroidism. This led her on a quest to heal herself, re-educating herself on health at the Institute of Integrative Nutrition in New York and becoming a Bulletproof health coach under Dave Asprey. She is now the Founder of Oxford Healthspan and Co-Founder of the non-profit organization, Oxford Longevity Project.

FAQs

See all FAQs or contact us!

What is spermidine?

Spermidine is a powerful polyamine that promotes autophagy, the body’s cellular “clean-up” process, and inhibits 9 of the 12 scientifically identified root causes of aging, known as the “Hallmarks of Aging.” While two-thirds of the body’s spermidine is produced by the gut and body tissues, the remaining third comes from food. As we age, natural spermidine production declines, so maintaining youthful levels requires external sources, either from spermidine-rich foods or supplements like Primeadine.

What are the benefits of spermidine?

Studies link higher levels of spermidine with longevity. Human trials show that food-derived spermidine supports cognition, heart health, hormonal balance, hair growth, collagen production, and nail strength, with potential benefits for fertility and circadian rhythm. These effects stem from spermidine's ability to trigger autophagy—the body's cell renewal process—and inhibit nine of the twelve "Hallmarks of Aging," including inflammation, stem cell and mitochondrial dysfunction, and gut imbalance. Clients also report deeper sleep, increased energy, gray hair reversal, improved skin, and better gut health. Read this blog post to learn more.

What makes Primeadine superior to other spermidine supplements?

While we can’t speak directly about the formulation of other spermidine products, here are some of the main differentiators of Primeadine®/Oxford Healthspan.

We source our raw materials from Japan, which is known for its Nobel Prize-winning scientific leadership on autophagy, or cell renewal. Japan has the most rigorous quality control and testing policies in the world, meaning our ingredients have the most advanced extraction process and meet the incredibly high standards of the Japan Health Food and Nutrition Food Association. They are tested for heavy metals, mold, fungi, and bacteria at the Japan Food Research Lab (JFRL), a third party independent testing lab.
Every single batch is tested for its amount of food-derived spermidine so we ensure it contains the minimum effective dose of 1mg stated on our labels.
Primeadine® is manufactured in Japan in an FDA-registered and -inspected facility with ISO22000 standards, the highest in food quality control. It is then encapsulated in an FDA cGMP facility in the USA and undergoes purity testing there as well at Eurofins or Delta.
Our capsules and tablets do not contain any synthetic ingredients, whereas other supplements typically contain magnesium stearate (of which circa 80% has hydrogenated fats in it; the supplement industry is not legally required to get rid of hydrogenated oils the way the processed food industry has been mandated by law to), shellac, talc and glycerin. Our products are all suitable for vegans. Learn more about our sourcing, quality, and testing standards.
The Primeadine® Original formulation includes a special type of prebiotic fiber, called FOS (fructooligosaccharide), that selectively feeds the friendly, spermidine-producing bacteria in the gut microbiome. The idea is to increase both supplemental, or 'exogenous' spermidine, as well as encourage your own body's natural ability to produce spermidine in your gut microbiome.
Primeadine® GF comes from a sub-strain of chlorella singled out from over 100 others because it alone contains a high level of spermidine and also contains putrescine, the precursor polyamine to both spermine and spermidine. Our chlorella is grown in the nutrient-abundant longevity islands of Okinawa, Japan, and exposed to sunlight to increase the chlorophyll and other nutrient content, such as vitamins D and K, which together help drive calcium to the bones. We combine the chlorella with two other anti-inflammatories and autophagy inducers, Okinawan turmeric and nobiletin (from Okinawan "Shikuwasa" citrus lime peel).
We do not use liposomes in Primeadine® because this is unnecessary for absorption and would prevent the benefits that happen when spermidine is exposed directly to the gut lining. There is no evidence that spermidine cannot be taken up by the cells on its own. Similar to amino acids, polyamines do not need a liposome to cross into the cell or to be taken up with epithelial cells. The process of creating a liposomal version also creates unnecessary expense.
We do not synthetically enrich our product with synthetic spermidine. Be wary of labels that say "wheat germ with spermidine" as this indicates that the wheat germ has been soaked in synthetic spermidine, thereby increasing the overall amount of spermidine but meaning it is no longer a natural source.
We do not use doses beyond what the European Food Safety Authority (EFSA) has mandated as safe for human consumption, which is 6mg daily. Please note that this is related to food-derived spermidine. Synthetic spermidine and synthetically enriched spermidine have never been tested in humans for safety or efficacy and are being sold without regulatory oversight.
We work closely with our scientific and clinical advisers at the University of Oxford and abroad, all of whom take our product and share it with their loved ones. Learn more about our scientific advisory board here.
We are also the only non-Japanese member of the Japan Autophagy Consortium, whose Senior Adviser is the 2016 Nobel Prize Winner in Medicine or Physiology, Prof Yoshimori Ohsumi, and whose Director is Prof Tamotsu Yoshimori, Osaka University. Prof Yoshimori conducted all of the mammalian research in autophagy that helped underpin Prof Ohsumi's work in yeast cells. Find out more about our story here.

What is the best spermidine dose to take?

The US FDA has not set a safe upper limit for food-derived spermidine, but the European Food Safety Authority considers up to 6 mg safe. Most studies use a daily dose of 1 mg of natural spermidine, along with spermine and putrescine, which are absent in synthetic versions. Synthetic spermidine has not been tested for human safety or efficacy.

Why is your spermidine supplement more expensive compared to other products I see on the internet?

We prioritize the highest quality, avoiding common additives like industrial seed oils, magnesium stearate, and talc often used in supplements. Unlike cheap synthetic spermidine often "cut" into products, we use food-derived spermidine sourced and manufactured in Japan under strict regulatory standards. Our products undergo rigorous third-party testing to ensure purity and effectiveness. This commitment to quality, like choosing the best ingredients for a child’s birthday cake, is our guiding philosophy.

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