NAC vs NAD vs
NR vs NMN? Due to the small alphabetical differences, these supplements are often
mixed up and confused by most consumers. We will cover the essentials and
explain about each of these supplements below.
NAD
NAD is derived from Nicotinamide Riboside (NR). The levels of NAD in our body
determine the speed of aging process. In younger cells and tissues, the levels
of NAD are higher. As a result, younger people tend to have better physical
activity, cognitive function and potential for cell repair and regeneration.
As we grow, the levels of NAD in our body start to decline. This is reflected
in the form of slowed cognitive response, loss of memory and reduced agility.
Related: Longevity and Anti Aging 101: What You Need to Know (A Comprehensive Guide)
Research suggests it may be possible to reverse mitochondrial decay with
dietary supplements that increase cellular levels of a molecule called NAD
(nicotinamide adenine dinucleotide).
NAD is a linchpin of
energy metabolism, among other roles, and its diminishing level with age has
been implicated in mitochondrial deterioration. Supplements containing
nicotinamide riboside, or NR, a precursor to NAD that's found in trace amounts
in milk, might be able to boost NAD levels. In support of that idea, half a
dozen Nobel laureates and other prominent scientists are working with two
small companies offering NR supplements.
The NAD story took off
toward the end of 2013 with a
high-profile paper by Harvard's David Sinclair and colleagues. Sinclair, recall, achieved
fame in the mid-2000s for research on yeast and mice that suggested the red
wine ingredient resveratrol mimics anti-aging effects of calorie restriction.
This time his lab made
headlines by reporting that the mitochondria in muscles of elderly mice were
restored to a youthful state after just a week of injections with NMN
(nicotinamide mononucleotide), a molecule that naturally occurs in cells and,
like NR, boosts levels of NAD.
NAD boosters might work
synergistically with supplements like resveratrol to help reinvigorate
mitochondria and ward off diseases of aging. Elysium is banking on this
potential synergy—its NR-containing supplement includes a resveratrol-like
substance called pterostilbene (pronounced tero-STILL-bean), which is found in
blueberries and grapes.
While resveratrol has hogged the anti-aging
spotlight over the past decade, unsung
researchers in places like Oxford, Miss., have quietly shown that pterostilbene is
a kind of extra-potent version of resveratrol. The pterostilbene molecule is
nearly identical to resveratrol's except for a couple of differences that make
it more "bioavailable" (animal studies indicate that about four times as much
ingested pterostilbene gets into the bloodstream as resveratrol). Test-tube
and rodent studies also suggest that pterostilbene is more potent than
resveratrol when it comes to improving
brain function, warding off various kinds of
cancer and preventing
heart disease.
How excited should we be about all this? If I were a middle-aged
mouse, I'd be ready to spend some of the nickels and dimes I'd dragged off the
sidewalk to try NR supplements. Even before Sinclair's paper, researchers
had
shown in 2012 that when given doses of NR, mice on high-fat diets gained 60 percent
less weight than they did on the same diets without NR. Further, none of the
mice on NR showed signs of diabetes, and their energy levels improved. The
scientists reportedly characterized NR's effects on metabolism as "nothing
short of astonishing."
But the paucity of human data gives me
pause. Nobel laureates notwithstanding, I plan to wait until more is known
before jumping up from the supper table to run out for some NR. Besides, it
probably won’t be long before more data come out given the growing buzz about
NAD.
NAD vs NAD+: What's the difference?
If you have done any research on aging and health recently, you have likely
stumbled across the so-called
anti-aging molecule, NAD. You have probably also seen it called NAD+ and maybe even as NADH. So,
what is the difference, if there is any?
The short answer is that
there is a difference, at least between NAD and NADH. Generally speaking, when
NAD is used, NAD is being talked about generally. And often when using “NAD”
it is referring to the specific chemical forms of NAD, NAD+ and NADH,
interchangeably.
NAD exists in two forms: NAD+ and NADH. Its
ability to switch between these two forms is what allows NAD to carry out its
main function—carrying electrons from one reaction to another in the process
of metabolism and energy production.
As an electron carrier, NAD+
and NADH help to convert the nutrients in your food into a form of energy your
cells can use.
NAC (N-Acetyl Cysteine)
Cysteine is a semi-essential amino acid. It’s considered semi-essential
because your body can produce it from other amino acids, namely methionine and
serine. It becomes essential only when the dietary intake of methionine and
serine is low.
Cysteine is found in most high-protein foods, such
as chicken, turkey, yogurt, cheese, eggs, sunflower seeds and legumes.
N-acetyl
cysteine (NAC) is a supplement form of cysteine. NAC is valued primarily for
its role in antioxidant production.
Glutathione vs NAC? Along with two other amino acids — glutamine and glycine —
NAC is needed to make and replenish glutathione. Therefore, N-acetyl
L-cysteine (NAC) is a precursor of glutathione, helps to replenish
intracellular glutathione, a vital cellular antioxidant. NAC has a low
molecular weight and is well absorbed via oral administration.
Glutathione
is one of the body’s most important antioxidants, which helps neutralize
free radicals that can damage cells and tissues in your body.
N-acetylcysteine (NAC) has a long history of use as a first-aid remedy for
acetaminophen poisoning. Emergency room physicians will administer it in cases
when you've taken an overdose of Tylenol or other acetaminophen products. The
way it neutralizes the toxic effects of the drug is by recharging glutathione,
thereby preventing liver damage.
GlyNAC vs NAC? GlyNAC is a patented combination of amino acids, Glycine and
N-Acetyl Cysteine. GlyNAC consists of two antioxidant precursors glycine
and N-acetylcysteine. Cells use these precursors to synthesize glutathione,
which is the most abundant antioxidant made by our own cells. Sekhar and
colleagues from the Baylor College of Medicine published a pilot clinical trial
in Clinical and Translational Medicine where they found that
supplementing aged adults with GlyNAC
improved physical function and cognition.
Related:
The similarity in terms of spelling with the only difference in one
character, these two popular nutrients are often mixed up and confused
by most consumers. However, scientifically these two molecules are
related to two distinctively different nutrients. NAC is related to
glutathione, an antioxidant whereas NAD is related to vitamin B
complex.
NADPH (also often confused with NAD) is responsible for generating free
radicals in immune cells by NADPH oxidase. These radicals are used to
destroy pathogens.
Hyperglycemia increases reactive oxygen species (ROS) and the resulting
oxidative stress plays a key role in the pathogenesis of diabetic
complications. Nicotinamide dinucleotide phosphate (NADPH) oxidase is one
of the major sources of ROS production in diabetes. In this study,
NAC inhibits NADPH oxidase activation in diabetes and reduces tissue oxidative damage
in all organs.
Nicotinamide Riboside vs Nicotinamide MonoNucleotide (NR vs NMN)
While most anti-aging products try to reverse signs of aging on your
skin, nicotinamide riboside — also called niagen — aims to reverse
signs of aging from inside your body.
There are multiple
precursors to NAD+, each with its own physiologic effects.
Nicotinamide riboside (NR) is a popular one with several notable
benefits over other precursors like niacin (NA) and niacinamide (NAM).
NA, for instance, may induce uncomfortable flushing, while NAM may
inhibit sirtuin at high doses, both undesirable effects.
Because of its unique profile of benefits and low risks, NR has
emerged as a popular choice, especially by its discoverer, biochemist
Charles Brenner, among the NAD+ precursors. In Scientific Reports,
researchers noted:
“Because NR does not cause flushing or inhibit sirtuins and the
genes (NRK1 and NRK2) required for the metabolism of NR to NAD+ are
upregulated in conditions of metabolic stress, NR has a particularly
strong potential as a distinct vitamin B3 to support human wellness
during metabolic stress and aging.”
“Therefore, administration of niacin or niacinamide is unlikely
to be widely adopted for maintaining health and function with aging,”
researchers wrote in
Nature Communications.
Within your body, nicotinamide riboside is converted into NAD+,
a helper molecule that exists inside each of your cells and supports
many aspects of healthy aging.
Nicotinamide riboside, or niagen, is an alternative form of vitamin
B3, also called niacin.
Like other forms of vitamin B3,
nicotinamide riboside is converted by your body into nicotinamide
adenine dinucleotide (NAD+), a coenzyme or helper molecule.
Nicotinamide
riboside supplements — such as niagen — have quickly become popular
because they appear to be especially effective at raising NAD+ levels
(
Source).
Nicotinamide riboside is also found in trace amounts in cows’ milk,
yeast and beer (
Trusted Source).
NR used to be considered superior because no
NMN transporter — required to get it into cells — had been detected. We now know
there is such a transporter, which gives NMN the advantage as it’s also
a more direct NAD+ precursor.
Most of the NAD+ precursor
research is done with NR. However, as you can see from the image above,
NMN converts to NAD+ whereas NR must first be converted into NMN before
it can be
converted into NAD+, so it makes more sense to use NMN for NAD+ augmentation.
Further, the Interventions Testing Program (ITP) tested NR and didn’t find a life extension effect (
Aging Cell 2021).
A study in 2022 suggests that
taking 250 mg/day of NMN can significantly increase and sustain the levels of NAD+ in the blood, without adverse side effects.
Niacin is also a useful supplement to use in increasing NAD+
levels. You just need to limit the dose to about 25 mg, which most is a
dose low enough not to cause any flushing. Higher doses are not likely
as effective as NMN and exercise in producing NAD+.
A meta-analysis (
Zhong 2022) was performed to investigate the effects of nicotinamide
adenine dinucleotide (NAD+) precursor supplementation on glucose
and lipid metabolism in human body. The main research terms of NAD+
precursors were Nicotinamide Riboside (NR), Nicotinamide Mononucleotide
(NMN), Nicotinic Acid (NA), Nicotinamide (NAM).
In this study, a meta-analysis based on currently published clinical
trials with NAD+ precursors showed that supplementation with NAD+
precursors improved TG (TriGlyceride), TC (Total Cholesterol), LDL (Low
Density Lipoprotein), and HDL (High Density Lipoprotein) levels in
humans, but resulted in hyperglycemia, compared with placebo or no
treatment.
Among them, NA (Nicotinic Acid) or Niacin has the most significant effect
on improving lipid metabolism.
As research grows, it is likely to become clearer that NMN and NR may
have differing benefits depending on the part of the body and their
use. Where NMN transporters are found, they could make one more
preferable over the other. NMN has also been found to improve insulin
activity and production which could help to accelerate metabolisms and
make the body more glucose tolerant.
That said, according to David Sinclair in this
podcast:
NAD is a big molecule relative to vitamin B3. It's got those
phosphates on there. It's got a sugar. It's got the vitamin B
attached. So you've got all these components that come together to
make this very complicated molecule called NAD. And when you give NMN,
it contains all three components that the body needs to make NAD. If
you give NR or just vitamin B3, which is an even smaller molecule, the
body has to find these other components from somewhere else. So where
do you get phosphate? Well, body needs it for DNA, needs it for bones.
So high doses of something that requires additional phosphate makes me
a little concerned, and we have compared NMN and NR head-to-head in
mouse studies. We've shown that NMN makes mice run further, old
mice can run 50% further because they better blood flow, better
energy. NR the same dose did not do that. In fact, it had no
effect.
Related:
Naturally Boosting NAD Levels
But there is good news. If you want to remain youthful and enjoy a long
and healthy life, then there are ways in which you can naturally enhance
the levels of NAD in your body. Continue reading to find out how:
1. Fasting - Fasting is practiced in many religions throughout
the world. In addition to its spiritual benefits, it turns out that
fasting is also beneficial for our health. Fasting, or reducing your
calorie intake is an excellent method for indirectly boosting the body’s
NAD levels. Fasting has been shown to increase the levels of NAD+ and
sirtuins; the proteins which have been found to slow the aging process.
While fasting is effective in increasing NAD+ levels, drastic reduction
in calorie intake or fasting can have a counterproductive effect. The
dangers of chronic undereating include muscle loss, bone density issues
and fatigue.
A safer strategy is temporarily restricting calories with
intermittent fasting (IF). There’s still a danger of under-eating, but IF
is more about limiting when to eat vs. how much you eat.
There is also some speculation that adopting a low carb-ketogenic diet
may also provide similar positive results.
2. Nicotinamide Riboside Dietary Supplements - Nicotinamide
Riboside (NR) has been discovered in Vitamin B3. No one really
paid attention to this molecule until research showed that our bodies
can use NR to metabolise NAD+! After this discovery, several NR
supplements became available in the markets. Various studies have shown
that NR supplements are beneficial in boosting the levels of NAD+ in the
body.
3. Exercise - Exercise is one of the easiest and most
cost-effective methods for boosting NAD+ levels. When we exercise, our
bodies need energy, which comes from NAD+. Basically, exercise forces
our body muscles to produce more mitochondria, which are the powerhouses
of cells. The increased production of mitochondria results in a natural
boost in NAD+ levels in the body. A
2019 paper in Physiological Reports
found that aerobic and strength exercise increased NAMPT levels in adults
over 55 by 28 and 30 percent respectively.
4. Too Much Sunlight May not be Good - Research has shown that
too much direct sunlight exposure can deplete the body of NAD+ levels.
This is because our body uses NAD+ to repair cells which get damaged as
a result of direct UV ray exposure from the sunlight. In case you feel
that excessive sunlight exposure is inevitable for you, then you should
wear sunblock, sunscreen or sunglasses.
5. Support methylationMethylation means adding methyl
groups to DNA, proteins, or other molecules. This process influences many
biochemical systems and functions in the body. One of these
systems is NAD+ production. Healthy methylation helps you recycle NAD+
(i.e., keep levels higher) through the aptly-named “salvage
pathway.” (
Nature 2020). A fundamental way to support methylation is to ensure you
get enough methyl factors like B12, riboflavin, and TMG.
6. Foods which Boost NAD Levels - There are certain foods which
can boost NAD levels in the body. Some of them include:
-
Dairy Milk – research has indicated that cow’s milk is a good source
of Riboside Nicotinamide (RN). A litre of fresh cow’s milk contains
about 3.9µmol of NAD+. So while you’re enjoying a refreshing glass
of milk, you’re actually getting younger and healthier!
-
Fish – here’s another reason for you to enjoy fish! some varieties
of fish like tuna, salmons and sardines are rich sources of NAD+ for
the body.
-
Mushrooms – many people like mushrooms and them as a regular food
item in their regular diet. But did you know that mushrooms,
especially the crimini mushrooms, also help in naturally boosting
NAD levels? Yes, that’s true. So, enjoy eating the mushrooms and
continue to look and younger and more youthful!
-
Yeast – yeast is an ingredient which is used for making bread and
other bakery products. Yeast contains Riboside Nicotinamide (RN),
which is a precursor of NAD. Here’s another reason for you to enjoy
your favorite pastries or buns whenever you visit the bakery! Enjoy
your favorite food while boosting NAD levels at the same time. How
cool is that!
-
Green Vegetables – green vegetables contain all sorts of nutrients
in them which are beneficial in a variety of ways. Recently, it has
come to light that green vegetables are also a good source of NAD
for the body. Some of these vegetables include peas and asparagus.
-
Whole Grains – as discussed earlier, Vitamin B3 also contains RN,
the precursor for NAD. However, when vegetables, food items or
grains are cooked or processed, they lose their nutrition as well as
the vitamin source. Therefore, it is recommended that you should
also eat raw vegetables and take whole grains instead of processed
foods.
-
Cut Down on Alcoholic Beverages – NAD is responsible for maintaining
the overall metabolic processes of the body. Alcohol tends to
interfere with these processes and reduce the efficacy of NAD.
Therefore, you should avoid excessive intake of alcoholic drinks
since they are also not good for your health.
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