THE SECRET NAD+ BOOSTING PROTOCOL

It’s no secret that people today are TOO FAT!

But it’s not just “fast food” that is to blame.

AS WE AGE, OUR LEVELS OF NAD+ DROP

By  age 60, we have 1/2 the NAD+ as  in our 20’s (21,57)

Declining NAD+ leads to metabolic dysfunction, age-related diseases and is a key contributor to the aging process(21,22,24,40,41).

high blood sugar -> inflammation -> low NAD+ -> disease and aging
As we age, this become a viscous circle
low NAD+ -> disease and aging -> less exercise -> higher blood sugar ->  increased inflammation

Understanding the role NAD+ plays in aging can help you REVERSE this circle and combat the effects of aging.
Not just weight and blood sugar levels, but Diabetes, Cardiovascular Disease, Cancer and even aging itself are influenced by lower NAD+ levels (21,22,40,41).

Now researchers  are discovering what  you can do to elevate your NAD+ levels to fight back

WHATS THE SECRET

There are several things  covered here that seem like a “Secret”, because they aren’t talked about by those just looking to sell pills or get clicks to their overhyped stories.

But I know that truly understanding this article can change people’s lives.   I’ll start with this one:

You DON’T have to take some pills to boost your NAD+

Just spend a little time learning about the science, so you can best tailor your nutrition and exercise plan to take advantage of the recent research breakthroughs and boost your NAD+.  A little, or a lot – it’s all up to you.

Having a well defined mental image of what increased NAD+ levels do for your health, rather than some vague idea of “it’s good for you”,  helps motivate people to stick to their diet and exercise programs.

And that is the goal of this post – to let you know there are many things you can do to raise your NAD+ levels to achieve a more youthful and energetic body.

WHAT TO DO

It’s pretty simple once you understand the science behind NAD+ and why it drops as we age.  The prescription is:

  • Periodic Carbohydrate Restriction – Ketosis
  • Exercise

A LITTLE KETOSIS

It’s well known that Calorie Restriction  (CR) can extend longevity by 30–50% in many mammals (32), but is not a realistic therapy  for most  humans.

Fortunately, you don’t have to starve yourself.

Researchers have found it is the production of ketone bodies, or Ketosis, that occurs when strict Calorie Restriction is imposed that provides the benefit in lowering inflammation and boosting NAD+ (3,9).

A Ketogenic Diet  is an easier alternative for putting the body into Ketosis than severe CR, and is great for boosting NAD+, but many people still find it difficult to adhere to.

Other research is finding that Intermittent or Periodic Ketosis is effective at extending lifespan and likely achieves much of the benefit(36,37).

Periodic Carbohydrate Restriction (PCR) or Fat Fasting is even easier to for most people to follow.

The goal is periodic ketosis, combined with HIIT to maximize AMPK and boost NAD+ levels,  restoring the healthy metabolism you had as a teenager. Weight Loss is just a side effect.

Even if you have no interest in changing your diet or exercise regimen, and only want to learn more about NAD+ and perhaps take a NAD booster supplement like Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN), you still need to read this page to better understand how critical it is to get your NAD+ up.

A LITTLE EXERCISE


Fortunately, it’s really just 1-2 hours a week.  Researchers are finding that 2-3  short bouts of High Intensity Interval Training  (HIIT) is far more effective at lowering inflammation (and increasing NAD+), especially among older adults (55)

Exercise is not actually required, but it is very effective at boosting NAD+, especially when performed at the right time – when blood glucose is low (see HIIT below, or here).

Hours a day of grinding endurance training does not boost NAD+ and can even be counter-productive (55).  You’re not trying to “burn fat”, but activate AMPK, which drives creation of NAD+.

 

INFLAMMATION DRIVES DISEASE AND AGING

Chronic, low-grade inflammation is recognized as a major characteristic of aging. This phenomenon is so pervasive that the term inflammaging has been coined to emphasize that many major age-related disabilities, including cancers, susceptibility to infections, and dementia have (31)

The 2016 publication Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity points out the central linkages between inflammation and aging.  “Longevity and aging are two sides of the same coin, as they both derive from the interaction between genetic and environmental factors.”

When we are injured, inflammation is the body’s first line of defense against invading microbes; but in old age inflammation attacks healthy tissues

Arthritis.  The old view of arthritis was that the cartilage that cushions and lubricates our joints wears away with years of use.  Now it is recognized that osteo-arthritis has the same roots as rheumatoid arthritis.  It is an auto-immune disorder, the body’s immune system turned traitor against our bones and cartilage.

Atherosclerosis.  The old view of coronary heart disease was that over many years, cholesterol deposits on the artery walls in the same way that mineral deposits build up inside a water pipe and gradually come to clog the pipe completely.  Now it is recognized that inflammation plays an essential role.

Cancer.  The old view was that there are random mutations  that cause the cells to disregard regulating signals from the body and just continue replicating and growing out of control.  Now we realize that cancer is a failure of the body’s immune defense system.  Cancer mutations themselves are not steady and random, but are ramped up as we get older by chronic, systemic inflammation.

Alzheimer’s Disease.  This is the latest paradigm to shift, highlighted in an this article in the MIT Technology Review about the work of Harvard Med School Professor Beth Stevens. Now we are beginning to see that glial cells  “go rogue” and begin—unexplainably—to destroy nerve connections that are healthy, even essential for the brain’s function.

Chronic inflammation is a direct cause or major contributor to  almost all aging-related diseases (456).
including:

  • heart disease
  • arthritis
  • cancer
  • diabetes
  • osteoporosis
  • Alzheimer’s
  • inflammatory bowel disease
  • asthma
  • obesity
  • sinusitis
  • COPD
  • atherosclerosis
  • periodontal disease
  • blisters
  • depression
  • lethargy
  • fatigue

 

read more about inflammation and aging here

HIGH BLOOD SUGAR INCREASES INFLAMMATION, LOWERS NAD+, AND SHORTENS LIFESPAN

Elevated blood glucose levels increase inflammation, contributing to disease and aging.

You can predict death more reliably by blood sugar level than you can by age.

The graphs indicate how blood sugar rises with age and how lifespan is related to blood sugar levels.

Studies have found blood glucose levels even at the normal range can have a significant impact on brain atrophy in aging. (Neuro Science News)

In Are We All Pre-diabetic, Life Extension Foundation journalist Kirk Stokel writes that people living in industrialized nations are experiencing an “epidemic of elevated blood sugar”:

One report evaluated 46,000 middle-age individuals and found more than 80% had fasting blood sugar of 85 mg/dL or greater.

Since incidence of disease starts to increase when fasting blood sugar rises above 85 mg/dl, this means the vast majority of aging humans today endure chronic cellular damage associated with elevated blood sugar.

The link between Blood Glucose levels and inflammation is well known and explored more here and here.

AS WE AGE, INFLAMMATION BECOMES THE KEY CONSUMER OF NAD+

Researchers are finding that as we age, decreased NAD+ levels lead to increased disease, illness, cancer and aging.

Researchers have also  found that increased systemic inflammation  as we age is the key consumer of NAD+.

Instead of taking pills that temporarily lessen the symptoms, with better nutrition and exercise we can dramatically lower the inflammation that destroys NAD+  and is the root cause for many of our illnesses.

WHAT IS NAD+

Boosting Your NAD+NAD+ stands for nicotinamide adenine dinucleotide.  From  simple bacteria to mammal including humans, Life as we know it cannot exist without  NAD+.

NAD+  is required for our mitochondria to burn glucose to power the basic functions of all our cells, and also plays a key role in signaling with our cells.

It has now been demonstrated that cellular NAD levels decline with age and disease.

This  decline impairs mitochondrial function, playing a crucial role in the development of metabolic dysfunction, age-related diseases and that this decline is both a consequence of and contributor to the aging process. (Braidy et al., 2011; Gomes et al., 2013; Massudi et al., 2012; Scheibye-Knudsen et al., 2014; Verdin, 2015; Zhu et al., 2015).

A vicious cycle exists in which molecular mechanisms involved in the aging process, such as oxidative stress, DNA damage, senescence, and inflammation, lead to tissue NAD decline which subsequently exacerbates the processes that caused its decline in the first place.

  •  NAD levels decline precipitously with aging in mammals and humans, and are strongly negatively affected by multiple disease and stress processes including obesity. At advanced ages these levels are a tiny fraction of what they are in young people.
  •  Maintaining a high level of constitutive NAD+ in the body is critical for maintaining health and functionality, for averting or reversing a number of deleterious disease phenomena, for energy and vitality, and possibly for extending life spans in humans.
  •  The rate of DNA damage increases significantly with aging, increasing demand for NAD+ for DNA repair. However in general, the reasons for age-related decline in NAD are not well understood.
  •  As a consequence of the above, inadequate levels of NAD can lead to a laundry list of disease processes, including type 2 diabetes, Alzheimer’s disease, and cancer. And to acceleration of aging.  Indeed, I venture an opinion that there is an unvirtuous cyclic process of interaction of the NAD-related feedback loops that manifests itself in the progressive acceleration of the processes of aging with aging itself – why we generally age faster and faster as we get older.
  • It has long been known that many deleterious disease phenomena can be prevented or reversed by promoting higher levels of NAD in animal models. There appears to be ample evidence that this approach is generally safe.
  •  Multiple strategies have been investigated for enhancing human levels of NAD, including enhancing its original synthesis in the body, downregulating biological processes that consume it, ingesting precursor molecules such as NMN or NR, and direct introduction of NAD into the bloodstream via IV.

Conclusion: As we age, declining NAD+ is a key contributor to illness, disease and deteriorating health

See more about NAD+ Benefits and research

WHAT DEPLETES  NAD AS WE AGE?

Our bodies do create NAD+ from Tryptophan in a 7 step process termed “de novo”.  But this is a very small quantity and not thought to fluctuate much depending on demand.

By far, the greatest source of NAD+ is thru the salvage pathway.  That is, recycled from NAM, NA, NR, or NMN.

The entire NAD+ pool is recycled nearly 3 times every day (r)!

When we are young and have high levels of NAD+, it  is mostly consumed as part of normal cellular respiration process – that is, oxidation of ATP for energy.

So where does all this NAD+ go when we age?  Does the salvage, or de novo creation pathways break down?  Not really.

The problem is, as we age there are more demands for NAD+ from 2 sources:

  • PARPs
  • CD38 and related Enzymes

PARPs repair damaged DNA strands, which increase as we age.  A popular aging theory holds that DNA damage is the cause of aging.

DNA damage is repairable, but PARPS consume up to 80% of available NAD+ in older humans, meaning it is a major cause of NAD+ shortage, leaving less NAD+ for cellular respiration, fighting inflammation, and disease.

PARP activity is reported to be a major consumption pathway for NAD+ (Pillai et al., 2005). Blocking PARP activity in- creases intracellular NAD+ (Bai et al., 2011; Pirinen et al., 2014)

CD38 is an enzyme that responds to inflammation.  As NAD+ levels drop while aging, CD38 levels rise in response to inflammation.  Its main function is consuming NAD+ (r)

As we age, demand for NAD+  from PARPs and CD38 greatly increases, leaving  less and less NAD+ for our mitochondria to perform the basic task of energy production.

No  wonder we have less and less energy as we age, and look at our grandchildren with such envy!

 In the normal operation of the NAD salvage cycle, NAD is conserved, shuttled back and forth between its two forms NAD+ and NADH.  In this process, NAD acts as a cofactor in a major metabolic cycle.  In other vital processes, however, NAD acts as a substrate and is consumed. It is quite possibly the case that age-related decline in levels of NAD are mainly associated with increased demand by those substrate processes with aging.

NAMPT 

NAD+ is constantly being created and consumed, with the entire NAD+ pool being  recycled every day, primarily through the salvage pathway (21,54)

NAMPT is the rate‐limiting enzyme in mammalian NAD+ salvage pathway,  converting Nam into NMN  as the first step  for maintaining NAD+(54)

Both, aging and obesity impairs NAMPT‐mediated NAD+ biosynthesis.(54)

Chronic inflammation induced by prolonged oxidative stress and inflammatory cytokines also reduce NAMPT and NAD+ levels in multiple tissues (54)

NAMPT is down-regulated by over-eating and sedentary lifestyle.  Obesity, high blood sugar levels, and  aging decrease NAMPT-mediated NAD+ biosynthesis (20,54).

Fasting and exercise up-regulate AMPK, which stimulates NAMPT to metabolize more  NAD+ (20,54)

Conclusion: NAMPT is the rate limiting enzyme necessary to continuously renew NAD+ .

AMPK CONTROLS THE AGING PROCESS

AMPK is both a sensing and signaling enzyme.  It senses ATP activity in the mitochondria – basically, energy levels.  When blood glucose levels are low, such as with CR or Keto diet, ATP activity is low and AMPK signals NAMPT to create more NAD+ (19)

The December 2011 e-publication AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network makes the point that control of Nrf2 along with control of other key pathways by AMPK drives aging.

Efficient control of energy metabolic homeostasis, enhanced stress resistance, and qualified cellular housekeeping are the hallmarks of improved healthspan and extended lifespan. AMPK signaling is involved in the regulation of all these characteristics via an integrated signaling network.

Many studies with lower organisms have revealed that increased AMPK activity can extend the lifespan.

Furthermore, inhibition of NF-κB signaling by AMPK suppresses inflammatory responses.

Emerging studies indicate that the responsiveness of AMPK signaling clearly declines with aging.

An increase of NAD+ levels followed by sirtuin activation is observed in situations of energy deficit, such as fasting (47), calorie restriction (CR) (47) or low glucose feeding (Fulco et al, 2008), and exercise (47,48).

On the contrary, multiple studies reported that high-fat high-sucrose (HFHS) feeding diminishes NAD+ content in liver (46,51), skeletal muscle (49), BAT (49), and white adipose tissue (WAT) (Yoshino et al, 2011).

Conclusion: AMPK senses low energy levels and responds by signaling NAMPT to increase intracellular NAD+ concentrations (18)

CALORIE RESTRICTION DECREASES INFLAMMATION AND EXTENDS LIFESPAN

Calorie Restriction  (CR) can extend longevity by 30–50%  and remains the surest path to increased longevity and resilience to diseases of aging across many organisms, from yeast to monkeys and perhaps humans (32).

CR  can lower the prevalence of age-related loss of function and multiple diseases, including tumors, cardiovascular disease, neurodegeneration, and  protects against diabetes, cancer, cardiovascular disease, sarcopenia, and neurodegeneration of certain brain regions in rhesus monkeys (31)

Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as “inflammaging.” Inflammaging is a highly signifcant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis [r]

CR decreases inflammation, which is believed to be the reason it protect against multiple diseases and extends lifespan.

In non-obese, healthy adults, 25%  CR  decreases inflammation with no significant adverse effect.

These CR-induced changes suggest a shift toward a healthy phenotype, given the established role of these pro-inflammatory molecules as risk markers in the development of metabolic syndrome and age-related chronic diseases, in particular CVD, T2D and cancer(1).

Conclusion: Calorie Restriction of 25% or more has significant effect at combating disease and aging – But, is difficult to follow for humans

DIETARY RESTRICTION

The definition of dietary restriction has been expanded from an alternative description of caloric restriction to also encompass a broader scope of interventions, including :

  • Periodic fasting
  • Fast Mimicking diet
  • Intermittent Fasting
  • Time-Restricted Feeding

These relatively novel interventions are reported to have beneficial effects on overall health and in some cases longevity.(34)

Both intermittent and periodic fasting can increase lifespan, even when there is little or no overall decrease in calorie intake(34)

When mice were given access to food for only 8–9 hours during the active phase of the day, metabolic diseases induced by a high-fat, high-fructose, and high-sucrose diet, were reduced without lowering caloric intake(34)

Ad lib feeding during the weekend did not interfere with the protective effects of time-restricted feeding(34)

Conclusion: Constant Calorie Restriction is not necessary.   Short periods of  deprivation provide the same benefits for health and life extension

KETOSIS

Ketosis is a metabolic state in which fat provides most of the fuel for the body.

It occurs when there is limited access to glucose (blood sugar), which is the preferred fuel source for many cells in the body.

Ketosis is most often associated with ketogenic and very low-carb diets, but can also  occur under Calorie Restriction, or any of the fasting methods mentioned above. (3, 4, 5, 6).

When carb intake falls below 50 grams per day, the lower blood glucose levels cause the Pancreas to signal the liver to process fatty acids, from the blood stream and from body fat, where they are processed into ketones to provide energy.

Glucose is usually the brain’s main fuel. However, unlike fatty acids, ketones can cross the blood-brain barrier and provide  up to 70% of the brain’s energy needs when glucose levels are low (3).

Conclusion: Ketones become the main source of energy for the body and brain when carb intake and insulin levels are low.

GLUCONEOGENESIS

Although most of the brain can use ketones, there are portions that require glucose to function.

On a very-low-carb diet, the liver can also switch on gluconeogenesis, which means “making new glucose”  from amino acids in protein, or from glycerol in triglycerides.

Gluconeogenesis increases metabolism to burn more calories (26, r).

Conclusion: On a very low-carb diet, up to 70% of the brain can be fueled by ketones. The rest can be fueled by glucose produced in the liver.

KETOGENIC DIET
The pie charts below show the typical nutrient breakdown of a low-fat Western diet, a low-carb diet and a typical ketogenic diet:
Carb, Fat and Protein Breakdown of Different Diets

The ketogenic diet is a popular weight loss diet that is well-supported by science (r).

In fact, many studies have found that ketogenic diets lead to much greater weight loss than low-fat diets (r, r, r).

In fact, research shows that the ketogenic diet is far superior to the recommended low-fat diets for weight loss. (2, 14, 15, 16).

What’s more, the diet is so filling that you can lose weight without counting calories or tracking your food (16).

One study found that people on a ketogenic diet lost 2.2 times more weight than those on a calorie-restricted low-fat diet. Triglyceride and HDL cholesterol levels also improved (17).

Another study found that participants on the ketogenic diet lost 3 times more weight than those on the Diabetes UK’s recommended diet (r).

What’s more, people tend to feel less hungry and more full on a ketogenic diet, which is attributed to ketosis. For this reason, it is generally not necessary to count calories on this diet (r, r).

A ketogenic diet also lowers risk for many diseases (8, r, r, 11, r, 13).

They are now being studied as a treatment for a wide variety of conditions (r):

  • Heart disease. Reducing carbs to achieve ketosis may improve heart disease risk factors like blood triglycerides, total cholesterol and HDL cholesterol (r, r).
  • Type 2 diabetes. The diet may improve insulin sensitivity by up to 75%, and some diabetics are able to reduce or even stop diabetes medication (r, r).
  • Metabolic syndrome. Ketogenic diets can improve all major symptoms of metabolic syndrome, including high triglycerides, excess belly fat and elevated blood pressure (r).
  • Alzheimer’s disease. A ketogenic diet may have benefits for patients with Alzheimer’s disease (r).
  • Cancer. Some studies suggest that ketogenic diets may aid in cancer therapy, possibly by helping to “starve” cancer cells of glucose (r, r).
  • Parkinson’s disease. A small study found that symptoms of Parkinson’s disease improved after 28 days on a ketogenic diet (r).
  • Acne. There is some evidence that this diet may reduce the severity and progression of acne (r).

Conclusion: Studies show that ketogenic diets lead to more weight loss than low-fat diets, and help with a number of chronic diseases, including metabolic syndrome, type 2 diabetes and Alzheimer’s.

FAT FASTING

A  report by the US Institute of Medicine’s Food and Nutrition Board states: “The lower limit of dietary carbohydrates compatible with life apparently is zero, provided that adequate amounts of protein and fat are consumed.”

In one study, a group of volunteers fasted for 84 hours (3.5 days), or  received a lipid infusion such that they got all the calories they needed.

The researchers found that there were no differences in “plasma glucose, free fatty acids, ketone bodies, insulin, and epinephrine concentrations” between fasting and non-fasting conditions (30)

The authors conclude, “These results demonstrate that restriction of dietary carbohydrate, not the general absence of energy intake itself, is responsible for initiating the metabolic response to short-term fasting.” (30)

Conclusion:  Calorie Restriction is NOT NECESSARY – Carbohydrate restriction provides the benefits

DON’T BE AFRAID OF “GOOD FAT”

For those that have a fat phobia, here’s 3 recent studies that may open your eyes a little.

Study 1:  Compared three different diets for weight loss: Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. (New England Journal of Medicine.)

The low-fat diet was calorically restricted, with a target 1800 calories a day for men, 1500 for women. It was 30% of calories from fat, and “participants were counseled to consume low-fat grains, vegetables, fruits, and legumes and to limit their consumption of additional fats, sweets, and high-fat snacks”.

The Mediterranean diet’s target calorie intake was the same as for the low-fat, but with a goal of 35% calories from fat, “the main sources of added fat were 30 to 45 g of olive oil and a handful of nuts (five to seven nuts, that’s it).

Thelow-carbohydrate diet was not restricted in calories; it was all you can eat. It provided “20 g of carbohydrates per day for the 2-month induction phase…, with a gradual increase to a maximum of 120 g per day to maintain the weight loss.

The intakes of total calories, protein, and fat were not limited.

The study lasted for 2 years; all participants were either overweight (BMI ≥27), or with diabetes or coronary heart disease.

Study 2: More proof that high fat, low carb diets are healthy found in this paper: A high-fat, ketogenic diet induces a unique metabolic state in mice.

This was was a high-fat diet, with 95% fat, 5% protein, and 0% carbohydrate.  When  animals were switched to this  diet they lost weight, lower glucose and insulin, and higher AMPK activity.

Study 3: Heres’ an interesting new study on the effects of keto diet on human muscles. The effects of ketogenic dieting on skeletal muscle and fat mass. One reason why it’s interesting is that the men in the study were already resistance-trained.

Twenty-six college aged resistance trained men volunteered to participate in this study and were divided into either:

  • VLCKD (5 % CHO, 75 % Fat, 20 % Protein)
  • traditional western diet (55 % CHO, 25 % fat, 20 % protein)

All subjects participated in a periodized resistance-training program three times per week

The ketogenic diet group gained 4.3 kg lean mass (muscle) compared to only 2.2 kg for the traditional diet group

The ketogenic group lost 2.2 kg of fat, compared to 1.5 kg in the traditional group.

Here’s some more articles that dispel the myths about Carbohydrates vs Fats in the human diet.

Carbohydrates, Not Saturated Fat, Are Correlated with Cardiovascular Disease

How Coconut Oil and other MCT’s aid weight loss

BHB THE KEY TO LIFE EXTENSION PROPERTIES OF CALORIC RESTRICTION

When the blood-glucose level drops  the liver generates glucose by breaking down glycogen. If glucose levels drop too much, the liver synthesizes ketone bodies as a sort of back up fuel source for use by other organs (4).

So, levels of ketone bodies  are elevated by starvation, caloric restriction, high-intensity exercise, or the low-carbohydrate ketogenic diet (5).

KETONE BODY β-hydroxybutyrate (BHB) INHIBITS INFLAMMATION

β-hydroxybutyrate (BHB) is one such ketone body of particular interest as it has unique properties in reducing inflammation (5).

BHB is not used solely as a energy source, but also acts as a signal to regulate metabolism when energy sources are low (5).

Due to this special role, only BHB suppresses activation of the NLRP3 inflammasome, a key driver of systemic inflammation.  Other ketone bodies such asAcAc,  butyrate and acetate do not have a similar effect on inflammation (5).

The ketone metabolite BHB blocks NLRP3 inflammasome-mediated inflammatory disease and mimics the life span extending properties of caloric restriction

 BHB AND NAD+

keto diet creates bhb to extend lifespan

A 2016 study found β-hydroxybutyrate significantly increased the phosphorylation of AMPK (16).

AMPK activation is the key signal that drives increased NAMPT, which is the rate limiting factor in the bodies constant recycling of NAD+ (r).

Metabolism of one BHB molecule require 2 molecules of NAD+ instead of the 4 molecules required in normal glucose metabolism, thereby preserving the cytoplasmic NAD+ pool (7).

  • Inhibits inflammation which is a key consumer of NAD+ as we age
  • Activates AMPK which drives endogenous production of NAMPT and NAD+
  • Uses 50% less NAD+ in the production of ATP for basic cellular energy

Studies in cells (r), animals (r), and patients (r, r) suggest that it may be useful in common neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases, as well as in insulin-resistant states, such as trauma, heart failure, and diabetes (r).

In humans, serum levels of BHB are usually in the low micromolar range but begin to rise to a few hundred micromolar after 12–16 h of fasting, reaching 1–2 mM after 2 days of fasting (r) and 6–8 mM with prolonged starvation (r).

Similarly, serum levels of BHB can reach 1–2 mM after 90 min of intense exercise (r). Consistent levels above 2 mM are also reached with a ketogenic diet that is almost devoid of carbohydrates (r).

Many aging-induced changes, such as the incidence of malignancies in mice (10), the increases in blood glucose and insulin caused by insulin resistance (11), and the muscular weakness have been shown to be decreased by the metabolism of ketone bodies (12).

In fact, research now points to the ketosis experienced by ketoegenic diet having the same life extension effects as caloric restriction, per this quote:

“The extension of life span by caloric restriction has been studied across species from yeast and Caenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis”

MCT Oil

MCT stands for medium-chain triglycerides, which are fats found in foods like coconut oil. They are metabolized differently than the long-chain triglycerides (LCT) found in most other foods.

Because of the shorter chain length, MCTs go straight to the liver where they are used as an instant energy source or turned into ketones.

This makes MCT oil an ideal energy source for those looking to cut down on carbs and maximize BHB ketone production (which should be EVERYONE)

MCT oil aids weight loss by:

  • Fat Storage: Given that MCTs are absorbed and used more rapidly than LCTs, they are less likely to be stored as body fat (10).
  • Burn Calories: Studies in animals and humans show that MCTs (mainly C8 and C10) may increase the body’s ability to burn fat and calories (12, 13, 14, 15, 16, 17, 18).
  • Greater Fat Loss: One study found that an MCT-rich diet caused greater fat burning and fat loss than a diet higher in LCTs. However, these effects may disappear after 2–3 weeks once the body has adapted (18).

In addition to weight loss, the increased production of ketones and decreased good sugar levels make MCT oil a increasingly popular therapy for disease control.

One study in children found that the MCT diet was comparable in effectiveness to the classic ketogenic diet in controlling seizures (23).

In one study of 152 people with Alzheimer’s disease, those who received an MCT supplement for 90 days had much higher ketone levels and a significant improvement in brain function compared to a control group (34).

One of the great things about MCT oil is that it has virtually no taste or smell, and doesn’t need to be refrigerated. So it is easy to add to protein shakes or bulletproof coffee.

Another great thing about MCT oil is the price.  This 32 ounce bottle  at  Amazon is around $24.  That’s nearly 9,000 calories in the bottle, which is the calories most people consume in 4-5 days.  So per calorie, its less $ than McDonalds!

Ketones, MCT oil, cancer, anti aging

Conclusion: MCT’s are quickly converted to Glucose for energy if needed, or converted to Ketones. They can increase BHB production even without dieting

 

NMN GREATLY INCREASES FAT METABOLISM

Administration of NMN improves mitochondrial fatty acid oxidation (33)

NMN-administered mice switched their main energy source from glucose to fatty acids (23)

EXERCISE INCREASES LIFESPAN


The best way to stay young really might be to keep moving. Research has shown physical activity can reduce inflammation in your body and improve heart health—both important for staying young beyond your years.

Aging results in chronic low grade inflammation that is associated with increased risk for disease, poor physical functioning and mortality. Strategies that reduce age-related inflammation improve the quality of life in older adults (1).

Regular exercise is recommended for older people for a variety of reasons including increasing muscle mass and reducing risk for chronic diseases of the heart and metabolic systems (2).

This recent study found that 4 hours of running per week increased average lifespan by 3 years.  Surprisingly, time spent running added more time that it took to run, with  each hour running adding  7 hours on average.

More about exercise and inflammation

HIIT

HIIT involves short bursts of intense exercise alternated with low-intensity recovery periods. Interestingly, it is perhaps the most time-efficient way to exercise (4, 5).

Typically, a HIIT workout will range from 10 to 30 minutes in duration (4).

Despite how short the workout is, it can produce health benefits similar to twice as much moderate-intensity exercise (6, 7).

This would be considered one “round” or “repetition” of HIIT, and you would typically complete 4 to 6 repetitions in one workout (4).

Regardless of how it is implemented, high-intensity intervals should involve short periods of vigorous exercise that make your heart rate speed up (4, 8).

This recently published study compares HIIT with resistance training and combined weights/cardio training. It found HIIT to be far more effective, particularly for older humans.

In some cases, the high-intensity regimen actually seemed to reverse the age-related decline in both mitochondrial function and muscle-building proteins.

  • High intensity interval training (HIIT), in particular sprint interval training (SIT), has been shown to  promote mitochondrial biogenesis
  • SIT is usually performed as very short sprints (20-30 s) at maximal intensity (“all out” effort) repeated 4-8 times.
  • As few as 4-6 sprints have been shown to increase mitochondrial biogenesis to a similar extent as long duration cycling (90-120 min at 65% of VO2max)
  • research  shows that it is more beneficial to undertake most training in a “low” glycogen state (Hansen et al., 2005) .

More about the  Benefits of HIIT

Read more about HIIT and Aging

EXERCISE AND CR INCREASE NAD+ PRODUCTION

It’s clear that the same things that help fight inflammation also increase NAD+.

AMPK is the reason why.  CR and exercise active AMPK, which stimulates NAMPT to metabolize more  NAD+ (20, 54)

Exercise, especially HIIT, activates the enzyme AMPK to increase your NAD+ levels, stimulate glucose uptake ad mitochondrial biiogenesis (31, 55)

Exercise while fasting is even more effective at cranking up AMPK to elevate your NAD+ levels (r).  Exercise while fasting, or continue to exercise after you “hit your wall” (55)

“Athletes have a 2-fold higher levels of NAMPT in their skeletal muscle compared with sedentary adults” (38

Exercise, especially HIIT, activates the enzyme AMPK to increase your NAD+ levels, stimulate glucose uptake and mitochondrial biiogenesis (31)

Exercise while fasting is even more effective at cranking up AMPK to elevate your NAD+ levels (r).

Conclusion: HIIT 2-3 times per week while in low blood glucose state is ideal for Activating AMPK and boosting NAD+

SUPPLEMENTS TO INCREASE NAD+

Studies show that high levels of NAD+ result in stronger, healthier cells and mitochondrial function. (r)

More importantly, their analysis revealed that mitochondrial dysfunction is reversible with NAD+ supplementation, enabling the life and health of cells to be prolonged  at the molecular level. (r)

NAD+ cannot be taken as oral supplements  because it does not survive the digestive system long enough to enter your cells (25).

However, researchers have found that the molecules our bodies use to make NAD+ can be taken as supplements and DO make their way through the digestive system where they  are processed (mostly) by the liver and DO raise NAD+ levels in the blood and organs.

These NAD+ precursors have been tested in mice and humans to evaluate their effectiveness at elevating NAD+ levels and treating various disease conditions. The NAD+ precursors are (25):

  • NMN – Nicotinamide Mononucleotide
  • NR – Nicotinamide Riboside
  • NAM – Nicotinamide
  • Niacin – Nicotinic Acid
  • Tryptophan

NAM, Niacin, and Tryptophan have been show to alleviate symptoms in a wide variety of disease, but have some drawbacks such as intense flushing (niacin), or inhibiting sirtuins (NAM).

The  landmark 2013 study by Dr David Sinclair  demonstrated that supplementation with NMN increased levels of NAD+  and reversed age related degeneration in mice, giving older mice the muscle capacity, endurance and metabolism of much younger mice – the “equivalent of a human 60 year old becoming more like a 20 year old” (24).

That study really lit a fire to research in the role NAD+ plays in regulating our metabolism and aging, with dozens of studies already completed and even more underway.

A later study by Dr Sinclair published in 2016 looked at the effects on health of long term (12 months) administration of NMN  on mice (23).  The following quotes are from that study:

NMN effectively mitigates age-associated physiological decline in mice

NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies

These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans

NMN is the precursor used by Dr Sinclair in all his experiments with NAD+ repletion.

NR was discovered in 2004 by Dr Charles Brenner, and is used in his experiments.

Perhaps just as importantly, they make it much easier for researchers to perform tests that explore the links between decreasing NAD+ and age related disease.

Conclusion: NAD+ levels can be increased by administration of NAD+ precursor molecules NA, NAM, NR, NMN, or tryptophan (25).

AMPK and NAMPT activators

With the realization of the profound impact that  boosting NAD+ levels has on health and lifespan, researchers are now testing thousands of natural products that may stimulate AMPK (60).

You might notice that many the SAME supplements that have the greatest positive impact  on health ALSO ACTIVATE AMPK.

This is further confirmation that the AMPK-NAD+ pathway is a key determinant of healthy aging (60)

  • Berberine has been shown to lower blood sugar levels as much as the leading prescription drug Metformin.  They may be equally effective at lowering inflammation thru their effect on blood sugar levels, but Metformin has been shown to lower NAD+ levels (r), so I would definately recommend Berberine.
  • Chlorogenic Acid (CGA), one of the active ingredients in Green Coffee beans, has prove to be a strong activator of AMPK (58).  CGA was also show to increase metabolism, lower blood sugar levels, and decrease risk of diabetes (59).
  • EGCG – EGCG activates AMPK, enhancing insulin signaling pathway by membrane translocation and phosphorylation of IRS-1, improving insulin sensitivity and secretion (60)
  • Curcumin
  • Sulforaphane –  strongly activates AMPK, and  has been shown to have numerous disease fighting and anti-aging potential(R).  Here is a  short list of studies showing Sulforaphane activating AMPK to fight Cancer(R),Diabetes(R),Obesity(R),Neurological disease (R),Heart disease (R),HIV (R),Colitis(R).

 

NAD BOOSTING PROTOCOL

-coming soon-

YOU CAN HAVE THE HEALTH AND ENERGY YOU HAD 10 or 20 YEARS AGO!

Yes, a bold statement, but I truly believe it is possible for most people.

Activate AMPK to boost NAD+

  • PCR (Periodic Carbohydrate Restriction) – 48 hours prior to HIIT sessions
  • HIIT (High Intensity Interval Training) – 2-3 short session a week, when blood glucose levels are at their lowest

Niagen and NMN clearly boost NAD+ levels, but you can  do a lot yourself.

 

REFERENCES:

  1. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans (Meydayni, 2016)
  2. A high-fat, ketogenic diet induces a unique metabolic state in mice. (Kennedy, 2007)
  3. Ketone body metabolism and cardiovascular disease.(Cotter, 2013)
  4. Ketone bodies as signaling metabolites(Newman, 2014)
  5. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease(Youm, 2015)
  6. The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study.(Guisado, 2011)
  7. β-Hydroxybutyrate: A Signaling Metabolite in starvation response(Morales, 2016)
  8. Physiological roles of ketone bodies as substrates and signals in mammalian tissues(Robinson, 1980)
  9. Ketone bodies mimic the life span extending properties of caloric restriction (Veech, 2017)
  10. Novel ketone diet enhances physical and cognitive performance(Murray, 2016)
  11. Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet.
  12. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes(Cox, 2013)
  13. Neuroendocrine Factors in the Regulation of Inflammation: Excessive Adiposity and Calorie Restriction (Fontana, 2009)
  14. Beta-adrenergic receptors are critical for weight loss but not for other metabolic adaptations to the consumption of a ketogenic diet in male mice(August, 2017)
  15. A randomized trial of a low-carbohydrate diet for obesity(Foster, 2003)
  16. β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation(Bae, 2016)
  17. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. (Maalouf, 2009)
  18. AMPK activation protects cells from oxidative stress‐induced senescence via autophagic flux restoration and intracellular NAD + elevation (Han, 2016)
  19. Regulation of AMP-activated protein kinase by natural and synthetic activators (Hardie, 2015)
  20. Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice (Yoshino, 2011)
  21. NAD+ metabolism: Bioenergetics, signaling and manipulation for therapy (Yang, 2016)
  22. NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. (Zhang, 2016)
  23. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice (Mills, 2016)
  24. Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging (Gomes, Sinclair,2013)b
  25. NAD+ metabolism and the control of energy homeostasis – a balancing act between mitochondria and the nucleus (Canto, 2015)
  26. Modulating NAD+ metabolism, from bench to bedside (Auwerx, 2017)
  27. Aspects of Tryptophan and Nicotinamide Adenine Dinucleotide in Immunity: A New Twist in an Old Tale. (Rodriguez, 2017)
  28. Effects of Exhaustive Aerobic Exercise on Tryptophan-Kynurenine Metabolism in Trained Athletes (Strasser, 2016)
  29. PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation(Bai, 2011)
  30. Carbohydrate restriction regulates the adaptive response to fastingCarbohydrate restriction regulates the adaptive response to fasting (Klein, 1992)
  31. Interventions to Slow Aging in Humans: Are We Ready? (longo, 2015)
  32. Extending healthy life span–from yeast to humans (longo, 2010)
  33. Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure (Zhang, 2017)
  34. Dietary restriction with and without caloric restriction for healthy aging (Lee, 2016)
  35. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity (Cato, 2009)
  36. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan (Longo, 2015)
  37. Diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms (Longo, 2016
  38. Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle (Porter, 2015)
  39. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice (Newman, 2017)
  40. NAD+ and sirtuins in aging and disease (Imai, 2014)
  41. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling.  (Mouchiroud, 2013)
  42. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice (de Picciotto, 2016)
  43. NAMPT- mediated NAD(+) biosynthesis is essential for vision in mice  (Lin, 2016)
  44. Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice (Williams, 2017)
  45. NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair( Fang, 2016 )
  46. Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease (Gariani, 2017 )
  47. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle(Canto, 2010)
  48. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity(Canto, 2009 )
  49. The NAD (+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity(Canto, 2012 )
  50. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans(Trammell, 2016a )
  51. Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice(Trammell, 2016b )
  52. NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtuins-AMPK-mTOR pathway (Zhuo, 2011)
  53. NAMPT-mediated NAD biosynthesis as the internal timing mechanism: In NAD+ World, time is running in its own way (Poljsak, 2017)
  54. THE EFFECT OF DIFFERENT EXERCISE REGIMENS ON MITOCHONDRIAL BIOGENESIS AND PERFORMANCE (Philander, 2014)
  55. Dietary proanthocyanidins boost hepatic NAD+ metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats (Aragon’s, 2016)
  56. NAD+ Deficits in Age-Related Diseases and Cancer (Garrido, 2017)
  57. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation (Ong, 2013)
  58. Chlorogenic Acid Improves Late Diabetes through Adiponectin Receptor Signaling Pathways in db/db Mice (Chang, 2015)
  59. Adenosine Monophosphate (AMP)-Activated Protein Kinase: A New Target for Nutraceutical Compounds (Marin-Aguilar, 2017)
  60. AMPK activation protects cells from oxidative stress‐induced senescence via autophagic flux restoration and intracellular NAD + elevation (Han, 2016)

 

 

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