Nicotinamide adenine dinucleotide, or “NAD” to its friends, is a coenzyme produced in the human body (amongst other places), and it is critical for cellular energy metabolism, but there’s more to it than that.

Today we’ll be looking mostly at NAD⁺, of which the + indicates the positive formal charge of one of its nitrogen atoms. We won’t get too much into the chemistry of this, but we will mention that it’s a cofactor with NADH—the former accepting electrons and the latter donating electrons.

Both NAD⁺ and NADH are critical to good health, but we’re going to focus on NAD⁺ for the simple reason that it gets depleted with aging.

Note: it gets depleted with aging.

Chronological age is not so important here, but there is a direct relationship between biological aging and NAD⁺ depletion.

For example, healthy centenarians tend not to have depleted NAD⁺ levels. Further, its depletion (in those in whom it is depleted) is then a causal factor for many age-related diseases:

❝Remarkably, ageing is accompanied by a gradual decline in tissue and cellular NAD⁺ levels in multiple model organisms, including rodents and humans.

This decline in NAD⁺ levels is linked causally to numerous ageing-associated diseases, including cognitive decline, cancer, metabolic disease, sarcopenia and frailty.

Many of these ageing-associated diseases can be slowed down and even reversed by restoring NAD⁺ levels.❞

~ Dr. Rosalba Perrone et al.

Read in full: NAD⁺ metabolism and its roles in cellular processes during ageing

As for restoring those NADᐩ levels, that does help in interventional trials, whether by supplementing directly, or with NAD precursors*:

❝NAD⁺ levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility.

Restoration of NAD⁺ levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules that hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan.❞

~ Dr. David Sinclair et al.

Read more: Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

*There are actually also other NAD-boosting molecules besides NAD itself and its precursors. For example, the liver will not produce NADᐩ unless it has aminocarboxymuconate-semialdehyde decarboxylase (or “ACMSD”, to its friends), which limits the production of NADᐩ. Why, you ask? The theory is that it is a kind of evolutionary conservativism, much like not lighting a fire without the ability to put it out. In any case, taking ACMSD-blockers will thus result in an increased endogenous production of NADᐩ.

You can read about this here:

De novo NAD⁺ synthesis enhances mitochondrial function and improves health

Nor is taking supplements or drugs the only way to get more of it; there’s an enzyme nicotinamide phosphoribosyltransferase (“NAMPT”, to its friends) involved in the synthesis of NADᐩ, and exercise boosts levels by 127% (i.e., it more than doubles the levels), based on a modest three-week exercise bike regimen:

Skeletal muscle NAMPT is induced by exercise in humans

And to underline that point, another study found that resistance training (so, a different kind of exercise from that of the previous study) boosts levels of NADᐩ itself by the same 127%:

Resistance training increases muscle NAD⁺ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals

One way to get more out of NADᐩ

We’ll get straight to the point: it works very well paired with a senolytic agent, i.e. something that kills aging cells so that they get recycled sooner:

NAD+, Senolytics, or Pyruvate for Healthy Aging?

To read more about senolytics, check out:

Fisetin: The Anti-Aging Assassin

Want to try some?

We don’t sell it, but here for your convenience is an example product on Amazon 😎

Enjoy!

Policosanol (which can be extracted from various sources, but is mostly made from sugar cane extract) is marketed as lipid-lowering agent for improving cholesterol levels, but its research history has not been without controversy:

2001: it works!

After a lot of research in the 1990s, it came out of the gate strong in 2001, with:

❝Policosanol (5 and 10 mg/day) significantly decreased LDL-cholesterol (17.3% and 26.7%, respectively), total cholesterol (12.9% and 19.5%), as well as the ratios of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (17.2% and 26.5%) and total cholesterol to HDL-cholesterol (16.3% and 21.0%) compared with baseline and placebo❞

This, by the way, is comparable in efficacy to the most powerful statins, but without the adverse side effects.

Source: Efficacy and tolerability of policosanol in hypercholesterolemic postmenopausal women

Furthermore, its effects were not limited to postmenopausal women, and additionally, it was found that 20mg/day was sufficient for optimal effects; 40mg worked exactly the same as 20mg:

Read: Effects of policosanol 20 versus 40 mg/day in the treatment of patients with type II hypercholesterolemia: a 6-month double-blind study

2006–2010: we do not trust the Cubans!

After it had been marketed and used in much of the world for some years, extra scrutiny was brought upon it, because the initial studies had been performed by the same lab in Cuba, a commercial lab that had tested them for a private interest (i.e., a company selling the supplement):

Heart Beat: Policosanol: A sweet nothing for high cholesterol

And furthermore, US-based labs were unable to replicate the results:

Policosanols as Nutraceuticals: Fact or Fiction

The Cuban researchers countered that the composition of policosanol as produced in their lab was different than the composition of the policosanol as produced in the US labs, because of the purity of the ingredients used in the Cuban lab.

Which, on the face of it, could be true or could just be the claim of a commercial lab with an association with a company selling a product.

Of course, importing Cuban ingredients to test them in the US was not a reasonably accessible option for the US-based labs, because of the US’s embargo of Cuba. In principle it could be done, but unless there is already a huge clear profit incentive, research scientists are usually on their hands and knees begging for grants already, so getting extra funding for specially-important Cuban ingredients was not going to be likely.

2012: never mind, it does work after all!

An American meta-analysis of 4596 patients from 52 eligible studies (from around the world, so many of them not affected by the US’s embargo; some were from within the US using non-Cuban ingredients, though), found:

❝policosanol is more effective than plant sterols and stanols for LDL level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy❞

Those last words there, to be clear, mean “yes, the original claim of being on a par with statins is at least more or less true”.

Source: Meta-Analysis of Natural Therapies for Hyperlipidemia: Plant Sterols and Stanols versus Policosanol

2018: also yes, the Cuban kind does get those extra-effective results, even when tested outside of Cuba

A Korean research team verified this; it’s quite straightforward so for brevity we’ll just drop links:

• Consumption of Cuban Policosanol Improves Blood Pressure and Lipid Profile via Enhancement of HDL Functionality in Healthy Women Subjects: Randomized, Double-Blinded, and Placebo-Controlled Study
• Long-Term Consumption of Cuban Policosanol Lowers Central and Brachial Blood Pressure and Improves Lipid Profile With Enhancement of Lipoprotein Properties in Healthy Korean Participants

Mystery resolved!

Want to try some?

We don’t sell it, but here for your convenience is an example product on Amazon—it’s not the Cuban kind, because the US’s trade embargo makes it difficult for the US to import even things that are theoretically now exempt from the embargo such as food and medicines. In principle they can now be imported, but in practice, the extra regulations added to Cuban imports make it nearly impossible, especially for small sellers.

Still, it’s 40mg/tablet policosanol from sugar cane extract, and 3rd party lab tested, so it’s the next best thing 😎

Enjoy!