What is NAD+ and what are the benefits of NAD supplements and NAD+

NAD+: is this new wonder supplement the secret to looking and feeling younger for longer?

May 23rd 2022 / Ingeborg Van Lotringen

This article is a repost which originally appeared on GET THE GLOSS

Edited for content. The opinions expressed in this article may not reflect the opinions of this site’s editors, staff or members.

Our Takeaways:

· NAD+ (nicotinamide adenine dinucleotide) is a naturally occurring cellular component.

· NAD+ is responsible for cellular repair as well as energy.

· Exercise and fasting can raise levels of NAD+ in the body.

MOVE OVER COLLAGEN THERE’S A NEW SUPPLEMENT WITH A GROWING FAN BASE PROMISING TO HOLD BACK THE YEARS. IS NAD MORE THAN A FAD? WE ASKED DOCTORS TO WEIGH IN 

Vitamin A, collagen powders, CBD… Not a month goes by when we hear about a new ‘wonder’ ingredient that is going to blitz our ailments and hold back the years. The latest contender is NAD+ (pronounced ‘N.A.D. plus’). Already crowding the shelves of health food stores in the US, where preventative medicine and supplements are an even bigger ‘thing’ than here (and a sign of what’s heading our way!), the energy-generating co-enzyme – a compound naturally found in the body – is beginning to make waves in the UK too.

The claim is that it may improve our health and, by extension, our skin, in a myriad of ways, from giving us more energy to reducing cravings to protecting against cell damage, and much more. It’s even touted as the ultimate anti-ageing pill for its ability to keep youthful energy levels topped up, with fans including biohacker Davinia Taylor. “It helps me get rid of brain fog and actually gives me a feeling of confidence. For me, it peps up my mood and changes my mental clarity, making me feel as if I’m 20,” she told us recently.

In the US, where it’s one of the fastest-growing and buzziest supplements, people have long stopped asking what is NAD+?. “They only want to know what the best supplement is,” says molecular biologist and UK supplement entrepreneur Dr Nichola Conlon. So will it prove to be the game-changer everyone’s looking for, putting a spring in our step, making us feel and look younger or even live longer?

The doctors we spoke to were open-minded. Cosmetic physician Dr David Jack, who has his own range of supplements says: “I’ve seen numerous studies in recent years showing benefits of NAD supplementation in modulating inflammation, metabolic decline and cellular and DNA repair,” he says. “Although the evidence is in its early stages, given the low chance of side-effects it may be a very useful supplement for patients either suffering from neurodegenerative conditions or as part of an anti-ageing supplement routine”.

Let’s investigate further…

What is NAD used for?

NAD+ (sometimes called NADH or NAD) stands for nicotinamide adenine dinucleotide, a natural chemical found in every single cell in the body. Think of it like a battery. It plays a major role in generating cellular energy, as well as in the maintenance and repair of our cells, including our DNA. It’s thought to be involved in more than 500 different reactions that keep cells in good health. No biggie, then.

How does NAD+ work to help fight ageing?

If we have high levels of NAD+, it means we have lots of cellular energy – our cells function optimally and we feel more energetic and alert. It also means the body can repair itself quicker, which helps keep our organs, including our skin, in pristine working order. But just like collagen, our levels of NAD+ decline with age. It’s thought they halve every 20 years, from the day we’re born. With age, the body becomes less able to generate it, plus older and naturally more damaged cells use up NAD+ stores at a higher rate. A downward spiral of NAD+ correlates with the onset of many of the complaints associated with ageing including wrinkles, memory loss, heart problems, dementia, Parkinson’s, vision loss, and more. NAD+ decline is seen as one of the nine main hallmarks of ageing, according to Conlon.

How to increase NAD+ levels

You cannot stop the decline of your body’s ability to produce NAD+, but you can slow down the rate at which the body uses it up. Basically, the healthier you are and the less damage your cells sustain from things like disease, stress, unhealthy lifestyle choices and an unhealthy environment, the more NAD+ you have available for keeping your organs in ‘homeostasis’, i.e. strong, healthy and ‘young’ for their age. So: a good old healthy lifestyle with lots of stress management is, as per usual, the best way to keep this important powerhouse ticking over. Conlon adds that research has shown that the well-known positive benefits of exercise and fasting are down to the fact that they ignite the body’s production of NAD+. “They create an energy stress in the body, which responds by increasing NAD+ to switch on cellular maintenance and repair in order to overcome this temporary strain,” she says. “HIIT and resistance training have been found to be the most effective.”

But in the States, and increasingly over here, supplementing NAD+ is thought to be a way of off-setting its natural decline as well. “Multiple studies have demonstrated that NAD+ boosting strategies have benefits at cellular, animal and human level,” says Conlon. One study suggests that one of the ways NAD+ supplementation can do this is by activating the protection and stabilisation of telomeres, which helps prevent cell death and therefore the risk of long-term diseases setting in. Ultimately, says Conlon, “while I would stop short of saying NAD+ boosters help you live longer, it is clear they improve healthspan, which is the proportion of your life you spend in good health.”

But there is a caveat. There have been thousands of papers written on NAD+ supplementation in animals, and about 20 human studies, says Conlon. But at present, there is no conclusive, long-term proof that it can reverse or delay ageing, and it is important to keep in mind that we are talking about a nutritional supplement here, not medication. That doesn’t stop people from leaping on the chance to try it, of course, preferring to take their chances in the pursuit of a longer, healthier life.

NAD+ benefits

With most of the evidence circumstantial, anecdotal, or based on animal studies, below are some of the things that NAD+ supplementation may be good for. It is prescribed in America (and increasingly, here) by functional medicine practitioners and nutritionists to aid in the recovery of these, but again, not as medication.

NAD to improve sports performance

Due to its energy-boosting abilities (many users report an increase in energy, resilience and recovery) and positive impact on muscle function, NAD+ is popular with athletes and sports performance coaches, says Paul Leadon, co-founder of UK supplement company Hinnao Technology. It is also used (in the US at least) to help treat chronic fatigue syndrome. “I know people use it to support mitochondria (the batteries of cells) so it’s good for those with fatigue,” explains nutritional therapist Daniel O’Shaughnessy.

NAD for sleep issues, hangovers and long Covid

In one study, it was shown NAD+ seems to re-set our internal ‘body clock’. So NAD+ supplementation is sometimes used by people who want to treat jet lag and insomnia. And because it fortifies cells’ defence systems, it is used by some as a hangover cure to help protect the liver from the damage alcohol does. As O’Shaughnessy comments: “it’s used in addiction to support the withdrawal from alcohol and some drugs. It’s also being researched for long-Covid support.”

NAD+ and skin ageing

The world of aesthetics and ‘tweakments’ is keeping a beady eye on NAD as well. No wonder, as high levels of cellular energy mean that the body can more effectively prevent and clear up signs of skin ageing such as brown spots and fine lines. “Not only that, but the basic principle of ‘tweakments’ is that a level of controlled damage is inflicted on the skin, which then sets off a repairing, collagen-boosting mechanism in the skin,” says Conlon. “However, if the body is low on cellular energy, it has trouble performing this tissue repair and it won’t generate much additional collagen, leading to disappointing or even negative results. Boosting NAD+ reserves is thought to shore up this collagen supply and can therefore be the essential missing ‘prep’ step in skin rejuvenation procedures.”

NAD and symptoms of menopause

The booming menopause market is also ready to pounce. “We are super interested in the implications for menopause relief, and are chasing scientific data for this,” says Dr Conlon. “Menopause causes a huge increase in cellular ageing in a short space of time, turning off the energy and repair mechanisms that you so desperately need right at this time of life.” She says the company has lots of anecdotal feedback on NAD+ supplementation having a major impact on how women feel when they take it to offset menopausal symptoms.

“NAD+ is good at mopping up DNA damage and oxidative stress,” says O’Shaughnessy. “Supplementing it may also support memory and cognition.” That means it could help with the dreaded ‘brain fog’.

NAD and fatigue

Cosmetic physician Dr Sophie Shotter says that in her experience NAD+ works to treat tiredness, especially hormonally-related fatigue. “I definitely notice the difference when I supplement; for starters, I don’t get that mid-afternoon energy slump.”

NAD and preventing cravings

Apart from the aforementioned protective effect on the liver and delivering much-needed energy when you’ve been burning the candle at both ends NAD+ can, according to Dr Conlon, “help suppress the cravings that plague addicts of all kinds.” The theory is that this is because having enough NAD+ in your system stops the body ‘running on empty’ from substance abuse. As a result, it craves fewer ‘fresh hits’ of more stimulants.

Biohacker and author Davinia Taylor, a recovering alcoholic, recently told us that she noticed that effect after having a NAD+ IV drip. “It gets rid of any cravings. Think sugar, shopping…. I didn’t even fancy the chips I was trying to treat myself with,” she said. “It shuts down the body’s addictive mechanism and its need for a dopamine rush. It makes me feel not high, not buzzy, not wired like you would from Red Bull – but chipper. It’s like an alternative to hair of the dog that’s actually good for you, and an antidote to the fact that hangovers get worse with age. It’s an awake, clean energy that helps you deal with any stress better; that’s one of the things we get worse at as we get older, and when our hormones are on their way out. This is the ultimate energy shortcut that works for me.”

NAD supplements: what is the best way to take NAD+?

NAD IV drips

Taylor gets her drips from GP Dr Enayat of London biohacking health clinic Hum2n, who offers a ‘substance detox programme’ of five IV drips in one week, starting at £2795, and a three-drip anti-ageing protocol from £1295.
Beware, though: apart from the substantial financial investment, having these drips is also an investment in time, as they typically take three hours to infuse. Unless you take the ‘speedy’ half-hour option which, according to people we’ve spoken to has an unpleasant side effect of feeling temporary stomach and brain pressure as the active works its way into your system.

The payoff, says Leadon, who’s had NAD+ IV drips himself, is a sustained high and clarity of mind. “Drips are great to prepare for a major event or to aid recovery,” he says. “But my preference is always to supplement in a way that’s as close as possible to what the body does naturally. So a little-and-regular approach in the shape of daily oral supplementation is, in my opinion, the best way forward for sustained overall age prevention and support.” He considers the liposomal NAD+ supplement he’s about to launch, will be the next best thing (of course) to an IV drip.

NAD+ liposomal drops

Getting NAD+ into your cells is tricky. “NAD+ is a very large molecule that cannot just penetrate the skin or the mucus membranes in the mouth [ie taken under the tongue] to enter the bloodstream,” says Leadon. “And taken as a capsule, it won’t survive the gut intact.” To get around the issue, Leadon has created a nano-sized version of NAD+ and stabilised it in a ‘liposomal’ delivery system (protected in microscopic lipid bubbles). It’s been shown to go straight into the bloodstream when you place some drops of it under the tongue. “NAD+ is also very sensitive to heat damage so the drops may have to be kept in the fridge,” he says. Currently, the company is in the process of doing third party testing to back up its claims.

Supplements that help the body make NAD+

According to Conlon, getting NAD+ into the bloodstream doesn’t mean it actually gets into the body’s cells. “Right now, there’s very little proof that it can, apart from some indication that it can permeate some neuronal [brain and nervous system] cells. The exact same, by the way, goes for NAD+ IV drips,” she says.

This is why most NAD+ supplements provide not NAD+, but NAD+ precursors (since you ask – nicotinamide riboside or niagen tryptophan, or nicotinamide mononucleotide – NMN). Unlike the whole NAD+ molecule, these are readily absorbed into the system, and the body then converts them into NAD+.

But as far as Conlon is concerned, this is not enough. “Every cell in your body is like a small factory that needs power to function,” she says. “But with age, these ‘cell factories’ sustain major damage, which means the fuel you supply them with leaches away.” For her, it means that a good NAD+ supplement needs to provide a blend of nutrients that help repair and maintain your cells, alongside the fuel for making NAD+. Her Nuchido Time+ supplement is an example of this and has just been subjected to a double-blind, placebo-controlled crossover study to prove its claims. “We’ve tested the blood of human volunteers and we’ve seen an increase in NAD+ of 242 per cent in 16 days, on the basis of taking six capsules a day,” she says.

Can you take NAD when pregnant?

NAD+ is vital for normal organ development in babies but the advice is to, out of caution, hold off on taking NAD+ supplements in pregnancy. An Australian 2020 study on animals concluded that supplementing with precursor NMN improved the quality of ovarian cells in adult mammals but it’s not known what effect it had on their unborn young.

Are there any side effects of taking NAD+?

From the research so far (which has been done mostly on animals, with a few human studies), very few contra-indications have been flagged for taking supplements with NAD+ precursors, they seem to be very safe ingredients. In the human studies, 1000-2000mg of nicotinamide riboside (one popular precursor) a day had no harmful effects – and most supplements contain 250-300mg a day. However long-term effects in humans are still relatively unknown.

The verdict: is NAD+ the next big thing?

She would say so of course, but Conlon believes it is. “Whether it was Covid that inspired it or not, consumers in the UK have really embraced the idea of long-term preventative healthcare much more than they did before, and they’re looking for solutions that really hold water,” she says. “We’ve seen the popularity of collagen supplements, but the proof is dicey and few people are prepared to take the amount of collagen supplementation required to really see a difference.”

“While the research is growing, the possibilities are far-reaching because cellular energy is at the heart of longevity,” says Dr Conlon. For her, NAD+ supplementation is a way to stay mentally sharp and physically active for as long as possible throughout what are set to be longer lives than ever before.

Dr Sophie Shotter believes in NAD+ supplementation as well: “ I do recommend NAD supplements to patients, often those struggling with hormone-related energy levels,” she says. “But it’s important to note that we cannot supplement NAD directly,” she says. “I opt for NAD+ precursors, but I believe it’s also important to support our cellular ability to produce NAD+ as it decreases with age.”

Dr Shotter supplements patients as well as herself through IV drips with NADH “not a precursor but the ‘reduced’ version of NAD+; it easily converts into NAD+” she explains. She’s also a fan of the Nuchido Time+ supplement. “The fact that it has additional ingredients designed to boost both the cells’ ability to produce as well as recycle NAD+ is a real bonus,” she says. “With consistent use, I believe [supplements] can be very beneficial.”

But despite his strong interest in biohacking, this is one hack that nutritional therapist O’Shaughnessy isn’t getting behind just yet. He feels it’s expensive and certainly not a magic bullet. “NAD+ therapy should just be used as a tool,” he says. “If you’re suffering from fatigue, then it’s vital you consider the functional elements. These include being over-stressed, tackling vitamin and mineral deficiencies (particular in vegan diets which are often lacking iron, vitamin B12 and protein), digestive imbalances, sleep hygiene, food sensitivities, toxin overload, and more.” Taking NAD+ supplements, he says “will be a drop in the ocean if there are all sorts of imbalances in the body. The priority should be on addressing these.”

If you want to invest in an energy supplement, “a vitamin B complex is a cheap all-rounder,” he says. “Common sense says that we should function with optimal energy without the need for NAD+.” Try Healthspan High Strength Vitamin B Complex, £8.99.

Will studies prove him right or wrong? IS NAD+ a fad or the key to helping us age better? We’ll have to wait and see.

 

 

 

Promising Anti-Aging And Longevity Molecules

Posted on Jan 11, 2022, 4 p.m.

This article is a repost which originally appeared on WORLD HEALTH.NET

Edited for content

Regenerative, anti-aging, and longevity researchers have been working to find molecules that can help to improve and/or extend both human health and lifespan. This article gathers information on some of the most promising molecules to extend human healthspan and possibly lifespan. There are also a few honorable mentions at the end of the article. 

This list is heavily influenced by the Interventions Testing Program (ITP). This program selects a variety of different molecules each year to see which ones will extend mice’s lifespan. They use mice that are genetically heterogeneous, all this means is that the mice are genetically diverse and therefore minimize the possibility that characteristics of a single type of mice would affect the results. They also run these experiments at three separate labs, this is to figure out if the results are true and reproducible. 

The first molecule is called glycine. When the Interventions Testing Program trialed glycine it led to a four to six percent increase in lifespan for both males and females. Now bear with me because we need to unpack this. Glycine along with another molecule called NAC (N-acetylcysteine) are building blocks for a powerful antioxidant called glutathione. In humans, the glutathione antioxidant system is maintained until around 45 years of age and then it declines rapidly. But in a 2021 human trial glycine and NAC supplementation for 24 weeks corrected the glutathione deficiency. By using glycine and NAC we can restore the glutathione balance, and now we’ve got human data showing a positive benefit for health. 

A 2021 human trial of a group of molecules called the combined metabolic activators (CMAs)  that do consist of glutathione precursors, use cuts the recovery time from COVID-19 by a whopping three days when compared to placebo. In that trial to support glutathione, they did use NAC but instead of using glycine, they used another molecule called serine. Serine is just converted into glycine by the body. Overall though for the first molecule, it’s actually a combination of precursors to rebuild glutathione. The combination of glycine or serine and NAC.

Next up is nicotinamide riboside. As part of the combined metabolic activators, it also included nicotinamide riboside to help rebuild a molecule called NAD. This is important because new research has come out showing that after the age of around 60 years old our metabolism appears to tank and NAD is central to our metabolism. By rebuilding our NAD stores, we’re hopefully helping to support our metabolism and therefore improve our resiliency against diseases. 

When the Interventions Testing Program trialed nicotinamide riboside it did not extend lifespan. But much of the excitement around nicotinamide riboside is not to do with its potential of lifespan extension, instead, it’s because we can support our metabolism with it, which can make us more resilient against metabolic attacks. For example, sunlight, alcohol, and time zone disruption, all these things attack our metabolism, and by taking the nicotinamide riboside we may be more resilient against these attacks and that’s possibly why we can see an improvement in the recovery time of COVID-19 patients. 

The third molecule is 17-alpha estradiol which is a non-feminizing type of estrogen. When the Interventions Testing Program trialed it, it extended male mice’s lifespan by 19%. To stress again this is a non-feminizing type of estrogen, this is important because estrogenic actions have been increasingly recognized to have potential health and anti-aging benefits. It’s not just males that seem to get a benefit from this molecule, in female mice, there’s a 20% reduction in body weight. We are very excited to read more human data about this molecule.

Moving on to the fourth molecule on the list we’ve got SGLT2i inhibitors. This is a class of medication that is routinely prescribed to type 2 diabetic patients. When the Interventions Testing Program trialed it, it extended male mice lifespan by 14%. In humans, a 2019 systematic review was published in The Lancet journal looking specifically at heart disease outcomes involving over 34 000 patients, and what we could see in this study is that SGLT2i inhibitors reduced heart attacks by 11% and reduced the progression of kidney disease by 45%. 

This medication works by encouraging the kidneys to pee out sugar, instead of that sugar remaining in the bloodstream, it’s eliminated out of the system. This is important because it blunts the peak blood sugar levels which may be a factor in the lifespan extension effects that we see from the Interventions Testing Program. The potential for this molecule is because as we age our kidney function declines even from our mid-20s, and we’ve got human data showing that for non-diabetic kidney disease patients this type of medication does delay the progression of kidney disease. So I do wonder whether this class of medication would be used to the wider population to slow down kidney disease and therefore extend healthspan.

The fifth molecule that there is excitement about is rapamycin. Rapamycin is the golden egg from the Interventions Testing Program. Over and over again when they trial this molecule it extends both female and male lifespan, and that is why I’ve chosen to study this molecule. In a clinical trial, I want to figure out if using rapamycin once a week combined with exercise gives even greater muscle performance benefits compared to just exercise alone.

There are also three other molecules that almost made the top five list. The first one is fisetin. Essentially as we age some of our cells stop dividing and they become senescent. Fisetin does hold the potential to clear away those old cells, and that’s important because those old cells don’t just remain dormant they also release all sorts of factors that can damage our body. The Interventions Testing Program as part of their 2018 group of molecules will be trialing fisetin, and the Mayo Clinic have turned their attention to running human fisetin trials.

The second honorable mention is alpha-ketoglutarate (AKG), this molecule generated quite the hype in 2020 where a mice trial showed a 16.6% improvement in lifespan. We are all eagerly awaiting more human data to come out on this molecule to see whether it will improve human health.

The final honorable mention is hyaluronic acid. The quantity of hyaluronic acid gradually declines as we age, and hyaluronic acid is a major component of the connective tissue of the body including our blood vessels, skin, and organs. In a 2021 human 12-week double-blind placebo-controlled study we can see that hyaluronic acid significantly improved skin elasticity. If hyaluronic acid can improve skin health (wrinkles and dry skin) maybe it can improve blood vessel health and other parts of the body. Additionally, hyaluronic acid may also be the underlying reason as to why the naked mole rat has such exceptional longevity.

There we have an evidence-based list of top promising anti-aging and longevity molecules. But it is worth mentioning that this article is only partial, there are many others being studied looking for that elusive “fountain of youth” to help improve the human condition. 

As with anything you read on the internet, this article should not be construed as medical advice; please talk to your doctor or primary care provider before making any changes to your wellness routine.

Content may be edited for style and length.

Materials provided by:

This article was adapted from a presentation by Dr. Brad Stanfield

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