by Nils Osmar. June 10, 2022. Medical disclaimer
I’ve been taking two sirtuin 6 activators, Gaia Herbs’ Black Elderberry Extract and DoNotAge’s SIRT6 Activator, for about six months.
I started taking them because of some studies showing that activating sirtuin 6 extends both the lifespan and healthspan in lab animals. Sirtuin 1 improves healthspan; Sirtuin 6 extends lifespan in laboratory studies.
This study, published in Nature Communcations, is a good summary: Restoration of energy homeostasis by SIRT6 extends healthy lifespan, For more information about the study, see: SIRT6 Overexpression Extends Lifespan in Mice:
From the Study:
A significant amount of data demonstrate the major role of SIRT6 in metabolism31.
SIRT6 represses glycolysis in an HIF1α-dependent manner32, thereby acting as a tumor suppressor by inhibiting the Warburg effect33. Liver-specific deletion of SIRT6 results in increased glycolysis, triglyceride synthesis, reduced β-oxidation, and fatty liver formation…
Importantly, these metabolic roles of SIRT6 were determined in young mice. Thus, given SIRT6’s major role in aging, the broader metabolic role of SIRT6 under fasting as well as the effect of SIRT6 overexpression on metabolism in the context of aging should be described.
Here, we show that overexpression of SIRT6, but not SIRT1, extends lifespan in C57BL/6JOlaHsd mice in both sexes. Overexpression of SIRT6 reduced the age-related metabolic decline in energy metabolism pathways and inhibited frailty by preserving hepatic NAD+ levels, GNG capacity, and maintenance of normoglycemia, key markers of healthy aging. These results emphasize the potential of targeting SIRT6 for maintaining energy metabolism and reducing age-related frailty.
Animal vs. Human Studies
The study I cited above is intriguing, but has the common problem of being an animal study, meaninng that we have to extrapolate the results to humans, which always has an element of uncertainty. Critics have pointed out that there’s no direct proof that activating the sirtuin 6 gene will make us live years or decades longer.
This is a valid criticism, but it’s also true of every anti-aging product. The reason we test on animals is that they have relatively short lifespans; it would take longer than a typical human lifespan to “prove” beyond doubt that a supplement or other protocol extends the lifespan in human beings.
The sirtuins are promising because they’re highly evolutionarily conserved; the same anti-aging pathways exist in humans, mice and other complex organisms.
How to Activate the SIRT6 Gene
You can activate the sirtuin 6 gene in a number of ways. One is to do a water fast for ten days or more.
Another is to take a compound called fucoidan, a natural organic compound found in some types of seaweed and brown algae. But just because you’re buying products that claim to contain fucoidan doesn’t necessarily mean that the products are fresh, or are from the right strains of seaweed, or that the sirtuin 6 gene will be activated if you take them.
A third way is to take a supplement that’s rich in cyanidin, found in berries. The largest quantity is found in elderberries.
Fucoidan and Cyanidin Supplements
When I originally became interested in SIRT6 activation, I started taking Doctor’s Best fucoidan supplement. It may have been having anti-aging or life-extending effect I wasn’t aware of, but I felt nothing when taking it. I don’t mean this as a put-down of Doctor’s Best; I take some of their other products and like them; but I stopped taking their fucoidan after two bottles.
I next tried Gaia Herbs’ Black Elderberry Extract. This is anecdotal of course, but I would say that I got a slight energy boost from taking it. This may have been because of some sirtuin gene activator or could have been because of the 4 grams of carbohydrates (as naturally-occurring fructose) in each teaspoonful. I avoid sugar (including fructose) as a rule and do feel a little energy boost when taking it.
I then added DoNotAge’s SIRT6 Activator, taking it along with the elderberry product and also adding 1 gram of NMN and 0.5 grams of NR (both also from DoNotAge). My reasoning is that the sirtuin genes are NAD dependent; they’re most effective if NAD levels are high in the body. NMN and NR are both effective NAD activators
Taking them together, I felt an immediate improvement in both my physical and mental energy. It went beyond the slight energy boost that I’d felt from taking the elderberry alone.
Testing SIRT6 Activation
What interested me about DoNotAge’s approach was that they had wild-sourced the seaweed it was derived from, and that, according to several statements made by their CEO, they test every new strain of seaweed or algae in Vera Gorbunova’s laboratory to make sure that it actually is activating the sirtuin 6 gene before including it in their product. (This was actually what made me switch over to DoNotAge.) If the strain they’re testing doesn’t activate the sirtuin 1 gene, according to their public statements, they throw it out it and try again.
The world of supplements is a kind of wild west in which quality varies widely. I’d be delighted to see every company follow suit and start testing all of their products to verify that (1) their supplements contain what they list on the label; (2) that the ingredients are pure, fresh and potent; and (3) that they’re effective for their intended purpose.
Some supplements bother me and I stop taking them; others seem to have no effect at all (at least that I can feel); others have positive effects and I keep taking them.
As I mentioned, I felt an improvement in my physical and mental energy after starting the above supplements (along with an array of other supplements I’d already been taking). (For a full list of my current supplements and when I take them, see this article.)
I had been taking DoNotAge’s SIRT 6 Activator along with Gaia’s Black Elderberry Extract for about two months when I noticed some changes in my body.
- One change was that the hair on my arms, chest and torso, which had gotten kind of white and wispy… my chest hair was looking a bit like the fly-away hair on Bernie Sanders’ head… had gone dark again, and was much more lush and thick than it was previously. Another was was that my sex drive increased during this period, and has stayed high.
I discuss some of these changes in this video:
A more recent change is that I have fewer aches and pains after hitting the gym. I had DOMS (delayed onset muscle soreness) for the first few months after I started working out; it went away shortly after I started taking SIRT6 Activator. I don’t know whether this is cause and effect, but it’s consistent with the known anti-inflammatory effects of fucoidan. See article: Fucoidan as bio-functional molecule: Insights into the anti-inflammatory potential and associated molecular mechanisms
I take lots of supplements, so I don’t know for sure whether these supplements alone were solely responsible for these changes, or whether it was the fact that I was taking it while also taking NMN, resveratrol, Ca-AKG, ashwagandha, and several other supplements, and eating foods high in compounds such as CoQ10 and spermidine, which made it so effective for me. But I had been taking those other supplements and eating those foods, for months; adding the sirtuin 6 activators was almost certainly a factor.
I do notice when I take it by itself that it’s mentally stimulating, kind of like having drunk or four cups of coffee. I’ve taken it at night and I slept fine, but usually try to take it in the morning along with NMN, resveratrol, TMG, and some other supplements related to raising NAD and activating the sirtuin genes. I’ll often take it before or shortly after taking a cold shower, as cold exposure is another way of activating the sirtuin (survival) genes.
Can Sirtuin Activators Make You Sick?
Concerns are sometimes raised that sirtuin activators, like other supplements, might throw the body out of balance. In my own case, I haven’t seen any evidence of this. But do like taking “supplement holidays’ now and then, in the form of taking a weekend off from all supplements; then I resume taking them on Monday. Every three months I do a five day water fast or fasting mimicking diet; I’ll often skip all supplements during these fasts.
In terms of the specifics of sirtuin 6 activators, elderberries (fresh from the plant) contain small amounts of cyanide. Are they still in elderberry syrup? According to this Healthline article, the answer is no. The author states:
However, commercial preparations and cooked berries do not contain cyanide, so there are no reports of fatalities from eating these. Symptoms of eating uncooked berries, leaves, bark, or roots of the elderberry include nausea, vomiting, and diarrhea (2).
Fucoidan supplements are derived from seaweed and brown algae. Some people have raised concerns that taking them could increase iodine levels in the body, and could in theory result in thyroid problems.
Iodine is beneficial in proper amounts, but it’s true that too much can be problematic. I don’t know of any studies showing that fucoidan supplements contain enough iodine to cause problems. (I’ve searched but have not found any studies validating that concern.) I eat a lot of Wakame (seaweed), use a naturally iodized sea salt, and take 2 capules of SIRT 6 activators a day; I plan to have my iodine checked in a few months; if it’s high I’ll cut back on the seaweed.
If you do decide to take fucoidan, whether it’s from DoNotAge, Doctor’s Best, or one of the other companies selling it — and also eat seaweed and use iodized salt and have other sources of iodine in your diet or supplements — I’d suggest keeping an eye on your iodine levels. We do need some iodine but if we get an excess amount, which could occur if we have several sources of iodine in our diets, it can cause health problems. As with anything, we need to aim to maintain a proper balance.
If you would like to try DoNotAge’s SIRT6 Activator, I’ve put information about a discount code below; it makes it a bit more affordable. Unfortunately I don’t have a discount code for Gaia at this time.
Discount Code: PATHWAYS
For a 10% savings on all of DoNotAge’s products, use the code PATHWAYS when making a purchase.