Autophagy has been in the news a lot in recent years. The word is derived from Greek and means “self-devouring” or “self-eating”. Autophagy is used to describe the human body’s process of reusing old and damaged cell parts. i.e., it is your body’s cellular recycling system.
The main reason for the increasing visibility of this word is because of the surge in popularity of caloric restriction, intermittent fasting and low carbohydrate diets. All of these can induce autophagy, as can exercise and hypoxia.
Autophagy and Hair Growth
Interestingly, autophagy can also affect hair growth positively. Perhaps not too surprising considering the number of health conditions that are impacted by inflammation and dysregulation of autophagy (and the related issue of senescent cells).
An interesting 2019 study from University of California Los Angeles (UCLA) found that hair growth can be initiated by small molecules that activate autophagy. The scientists found that:
“Quiescent (telogen) hair follicles can be stimulated to initiate anagen and hair growth by small molecules that activate autophagy. Including the metabolites α-ketoglutarate (α-KG) and α-ketobutyrate (α-KB), and the prescription drugs rapamycin and metformin.”
Another more recent study from 2021 found that impairment of autophagy could be a potential mechanism in androgenetic alopecia. Interestingly, RIKEN (Japan) was involved in this research.
Yet another study from 2018 concluded that autophagy plays an essential role in human hair growth. Monasterium Laboratory was involved in this work.
Metformin, Rapamycin and Autophagy
In the first of the studies I listed on top, it is mentioned that metformin and rapamycin both impact autophagy via inhibiting mTOR and AMPK signaling. I have covered both these well known drugs in some of my past posts related to longevity and anti-aging.
While metformin is taken by diabetics, a large number of non-diabetics (including Dr. David Sinclair) who are trying to increase their healthy lifespan also take the drug. One major observational study of 200,000 patients from 2014 found that diabetics who take metformin actually outlived non-diabetics. However, this study does not imply causation. Therefore, longevity experts are eagerly awaiting results of the Targeting Aging with Metformin (TAME) trials.
You might have no interest in such esoteric findings that are usually only tested in mouse hair initially. However, caloric restriction (under professional guidance) and exercise are almost certainly going to improve your overall health. And caloric restriction even grows hair/fur in mice (of course).
Even if you see no reduction in hair loss, experimenting with such longevity related strategies is not a bad idea. I am very averse to taking drugs, but there is a good chance that I will get on metformin in the coming years. Not yet sure about rapamycin.
Update: March 2023 — Dr. David Sinclair credits four habits that have made his biological age a decade younger. These include: supplements, intermittent fasting, less stress, and exercise. He now eats an entirely plant based diet.
Update: December 2022 — The US FDA recently announced that NMN can no longer be classified as a new dietary ingredients (NDI) supplement. This means that it is not allowed to be sold in supplement products anymore. However, the enforcement of this ban seems to be nonexistent at the time of this update. Edit: Amazon bans NMN for use as a dietary supplement as of February 16, 2023.
Dr. Sinclair gives us his thoughts on the FDA’s new regulations governing the marketing and sales of NMN as a supplement to boost NAD levels.
Update: April 2022 — In his interesting new Lifespan with Dr. David Sinclair Podcast, a recent episode covered “NMN, NAD, NR, Resveratrol, Metformin & Other Longevity Molecules.
Dr. Sinclair recently added Spermidine to his protocol; became vegetarian (while still fasting and eating just once per day); lost 15 pounds; and entirely quit alcohol. So we now know that Dr. David Sinclair’s current supplement list in 2022 includes the following:
NMN (1g per day in the morning with yogurt).
Resveratrol (0.5 mg per day in the morning with yogurt).
Metformin (1g per day at night).
Statin (for cholesterol control).
Most importantly, the February 9 , 2022 podcast covered hair loss and grey hair in detail. It seems like the doctor trusts the studies that tout the benefits of laser hair growth devices and PRP.
Update: June 18, 2021 — New episode of David Sinclair on the Joe Rogan show. Besides NAD and NMN, they also discuss intermittent fasting.
Note that NAD stands for Nicotinamide Adenine Dinucleotide . And NMN stands for Nicotinamide Mononucleotide (NMN).
Also make sure to follow the developments of MIB-626, a NAD+ precursor that is currently in clinical trials.
Update: April 2020 — A new paper from China concludes that NMN is a promising molecule for therapy of various diseases. Likely via the targeting of NAD+ metabolism.
Update: January 14, 2020 — Dr. David Sinclair is participating in a Reddit AMA on January 14th from 4-6 pm EST. Official link. He will cover NAD, NMN, NR and resveratrol supplements. I hope someone asks Dr. Sinclair about his 80-year old father’s hair quality (the latter takes NAD supplements).
Update: In September 2019, Dr. David Sinclair made yet another appearance on the Joe Rogan show. Besides discussing his new book “Lifespan” and NAD plus NMN, he also talked about metformin in greater detail. He also discussed HGH, rapamycin, caloric restriction and fasting for longevity. On a related note, make sure to read my past post on TA-65 and Telomerase.
Update: In January 2019, Dr. David Sinclair made an appearance on the Joe Rogan show. He discussed NAD and other supplements in there. Also, in a recent Linkedin post, Dr. Sinclair said that his own regimen and NMN dosage was pretty simple: “I take 750 mg of NMN every morning, along with a gram of resveratrol and 500 mg of metformin.”
I first mentioned Harvard University’s Australian professor Dr. David Andrew Sinclair in several posts in 2016 and 2017. At that time, he presented some groundbreaking findings regarding anti-aging research in relation to increasing declining Nicotinamide adenine dinucleotide (NAD or NAD+) levels in aging humans. He is also renowned for his lab’s research on resveratrol. Make sure to also check out Dr. Sinclair’s AMA on reddit.
Nicotinamide Adenine Dinucleotide (NAD)
Nicotinamide Adenine Dinucleotide (NAD or NAD+) is a cofactor and coenzyme that is found in all living cells. Levels and bioavailability in humans decrease with ago. In December 2019, Dr. Sinclair posted a link to new research on real-time NAD biosensors.
NAD versus NAD+
Note that NAD and NAD+ are not exactly the same thing. The latter it the oxidized version of the former. It is also written as NAD+ via the superscript in technical articles. Time magazine had a lengthy article on NAD+ in 2018. The NAD+ co-enzyme is largely synthetized through NMN.
NAD versus NADH
NAD+ and NADH are two different forms of the coenzyme nicotinamide adenine dinucleotide (NAD). NADH is the reduced form of NAD, while NAD+ is the oxidized form. NADH stands for nicotinamide adenine dinucleotide hydrogen.
Dr. David Sinclair states that his team does not recommend people taking NAD precursors, since they have not yet been formally tested for safety.
However, on Amazon, it looks like NAD+ pills can be purchased legally, and they seem to be a form of Vitamin B3 (brand name Niagen). A company named Tru Niagen also sells them directly. A company named Alive by Nature also sells sublingual NAD+ and NMN online. Dosages can vary for most of these supplements.
Elysium Health is another popular company selling NAD+ supplements under the name “Basis”. The US FDA approval process for a new NAD or NMN related drug is extremely lengthy and expensive. So most companies are instead focusing on supplements.
Best NMN Supplements
While NAD itself is difficult to administer directly to humans, its precursors — nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) — are promising natural compounds to test in humans.
MNN supplements such as the one on the right are especially popular online and at GNC. However, make sure to read customer reviews in detail to make sure that there are long term benefits. Some people might just be experiencing placebo short term benefits. NMN supplements can come in pill, tablet, capsule and powder forms.
Nicotinamide riboside (also called Niagen) is an alternative form of Vitamin B3. It has been touted to reverse grey hair, wrinkles, hair loss and various other signs of aging. Thorne Research makes a popular combination version of nicotinamide riboside with resveratrol and cofactors. Tru Niagen also makes popular NR supplements.
Also see this article on Nicotinamide riboside (NR) vs. Nicotinamide mononucleotide (NMN).
NAD and its Precursor NMN
Human trials for both NAD and its precursor NMN have been underway in recent years. This will allow for more conclusive evidence in regards to both benefits and side effects in the near future. For now, it is wise to exercise caution when it comes to NAD and NMN supplement related potential side effects.
In regards to side effects, some cancer cells depend on NAD+ for sustained and rapid growth. So rather than increasing NAD levels to live longer, one may need to decrease them to fight cancer.
Dr. David Sinclair has formulated a capsule version of a precursor to NAD+ called Nicotinamide mononucleotide (NMN). This precursor is a naturally occurring compound that is found in small amounts in fruits and vegetables such as broccoli, cucumber, avocado and edamame.
David Sinclair, Resveratrol and Sirtuins
Dr. David Sinclair has all the credentials of a reputable and brilliant scientist. For well over a decade, he has promoted the benefits of resveratrol, which is found in small amounts in red wine, grapes, berries and other related fruits. Resveratrol switches on the well known anti-ageing gene Sirtuin-1. Both NAD and sirtuins are necessary for healthy aging, longevity and DNA quality.
Dr. Sinclair has conducted significant research on how sirtuins are modulated by endogenous molecules as well as pharmacological agents such as resveratrol. Other areas of anti-aging research in which Dr. Sinclair has participated include senolytics and caloric restriction.
However, many of Dr. Sinclair’s peers accuse him of being overoptimistic and impatient. Not always a bad thing in the hair loss world, where we typically have the opposite situation. The resvertarol angle has had some hiccups over the past decade and Dr. Sinclair seems to have shifted his focus to other anti-aging research in recent years.
Dr. Sinclair is using his own NAD molecule. He has supposedly reduced his biological age by 24 years after taking the pill.
David Sinclair’s father is 79 years old, and has been white water rafting and backpacking since starting to ingest the molecule a year-and-a-half ago.
Dr. Sinclair’s sister-in-law is now fertile again after taking the pill. This despite that fact that she started to transition into menopause in her 40s. (My note: I assume this implies that she is in her 50s now).
Potential increase in human lifespan to 150 years of age.
The pill leads to a decline in age related hair loss. (My note: Ironically, I find this to be the most believable of all the above fantastical claims. Even though hair loss is as yet almost impossible to cure in most people. New hair growth in bald regions of the scalp is especially difficult.
Human trials still two years away, but Dr. Sinclair aims to release the product into the market in five years.
David Sinclair Companies
Dr. Sinclair is the co-founder of a number of biotechnology companies (Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, Liberty Biosecurity). He is also the founder of Life Biosciences LLC, a longevity startup. And he is a scientific adviser to many companies, including InsideTracker.
Note: make sure to not confuse Dr. David Sinclair and Dr. Rodney Sinclair (who is also from Australia). The latter is a well known dermatologist and hair loss expert, who I have covered a few times on this blog.
Edit: I posted links to some critiques of Dr. Sinclair earlier in this post. A reader also posted this new one that is worth a read.