Jan
04
2020

Preserving Youthful Power

Dr. Christopher W. Shade (PH.D.) presented a lecture in Las Vegas on Dec.13, 2019 talking about preserving youthful power. The presentation was at the 27th Annual World Congress on Anti-Aging Medicine and his title was “Building Youthful NAD+ Power with Precursors, Sirtuin-Activating Compounds, and Methylation support”.

In the first place, nicotinamide adenine dinucleotide (NAD+) is a signalling molecule between the DNA of the nucleus of cells and the energy producing mitochondria that reside in the cells. The exact nature of the interaction is described in this review article. It describes how stress leads to a depletion of NAD+ and sirtuins, and causes accelerated aging. On the other hand, calorie restriction and exercise lead to increased production of NAD+, activation of sirtuins and longevity.

Details about low NAD+ activity

It is important to realize that when NAD+ is below a critical level the following disease states can develop. First, in the brain it is Alzheimer’s disease and neurodegenerative disease. Second, in the eyes macular degeneration and keratoconjunctivitis sicca can develop. Third, severe plaque-type psoriasis can occur in the skin. Fourth, the pancreas develops hyperinsulinemia and metabolic syndrome. Fifth, type 2 diabetes can make your muscles weak. Sixth, sarcopenia with loss of muscle mass and cardiovascular disease in the heart can also develop. Seventh, the liver reacts to the metabolic syndrome by causing hepatic steatosis. Metabolic syndrome causes inflammatory cytokines in the fatty tissue. Eighth, the lungs react by developing chronic obstructive pulmonary disease. Ninth, your blood can get endotoxin-induced inflammation and sepsis from bacteria. A lack of NAD+ causes all of these negative changes simultaneously in the body.

In fact, when a person exercises regularly, uses intermittent fasting as a tool of calorie restriction and takes supplements of NAD+ all of these negative processes stop and sirtuins are activated restoring the body to a more youthful condition.

Summary about the effects of NAD+

In other words, NAD+ is important for cardiometabolic health, energy balance, liver health, immune health and cognitive health. NAD+ is also involved in maintaining the membrane polarity of cell walls. The blood /brain barrier and the gut/blood barrier are also kept intact by NAD+. In addition, NAD+ is involved in detoxification and control of the action of free radicals. It also is important to control Inflammation. For these reasons, it is not a surprise that people with normal NAD+ function will be healthier than those who have a problem with this.

Sugar reduces NAD+ to NADH

It is important to note that scientists could show in animal models and in humans that sugar overconsumption leads to the reduction of NAD+ to NADH. All of the negative effects described above for low NAD+ are then coming true. NADH is a reduced and disabled form of the oxidized NAD+. In essence, this substance has no biological action.

Energy metabolism

Biochemists have determined with regard to the energy metabolism of mitochondria that there are three occasions where enzymes are dependent on NAD+. Without NAD+ the energy-providing oxidative metabolism in mitochondria would not take place. As NAD+ is lower in older age, this explains why an aging population has less energy. In addition, as we age, the number of mitochondria per cell is decreasing. That is to say that an aging population has less energy than youthful people.

Other factors that are important in preserving youthful power

The AMPK signalling pathway

AMPK stands for 5′ AMP-activated protein kinase. This is an enzyme that consists of three protein portions. In humans it is expressed in liver, brain and muscle tissue. It provides energy in the liver by fatty acid oxidation. In muscles it stimulates glucose uptake and fatty acid oxidation. AMPK also inhibits cholesterol synthesis, lipogenesis and triglyceride synthesis. Fasting and exercise can stimulate AMPK production, which in turn will stimulate SIR1 genes and NAD+ production. This is especially happening in muscle tissue. To put it another way, there are a close-linked metabolic reactions between NAD+, AMPK and sirtuins.

Balance between AMPK, NAD+ and methylation

Given the right circumstances this can lead to detoxification, longevity and energy. This is what intermittent fasting and exercise can do for you. AMPK needs high NAD+ levels to give you all of the benefits. But NAD+ must be balanced with methylation. This is a somewhat difficult subject to explain, but the link explains it in somewhat technical terms. In other words, with a balance of the body’s biochemistry the person is healthy. When there is a disbalance, you get sick.

Practical application how to supplement for preserving youthful power

Dr. Shade asked the rhetorical question: how can we achieve a balance between NAD+ and methylation?

His answer is to supplement with the following supplements.

  • Trimethylglycine (Betaine) 2‐5g/day
  • Vitamin B2: 10‐30mg/day
  • SAMe or methylcobalamin 1000‐3000mcg/day
  • Measure Homocysteine as marker of methylation; if it is low, the methylation pathway is normal and there is balance.

Next: how to we raise NAD+? The answer is by cardio-metabolic blending.

  • Berberine and quercetin (they are respiratory chain modulators)
  • Resveratrol, silymarin and lipoic acid (they are liver kinase B1 activators)
  • Resveratrol or pterostilbene and quercetin (they are sirtuin activators)
  • Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) 200- 400 mg per day
  • Trimethylglycine (Betaine) 2-5 grams per day and methylcobalamin, B2, and others (methylation support)
Preserving Youthful Power

Preserving Youthful Power

Conclusion

It is difficult to describe energy flow in biochemical terms. Dr. Christopher W. Shade did exactly that in a lecture he gave at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec.13, 2019. The key for preserving youthful power is to balance the metabolism that occurs in the nucleus of the body cells with the metabolism taking place in the mitochondria. The mitochondria are the energy producers, but the steering of this occurs through the metabolic products from the cell nucleus. NAD+ plays a key role in our energy metabolism. But there is an interplay with AMPK, which stands for 5′ AMP-activated protein kinase. Sirtuin genes interact with these messenger molecules as well and this is where longevity comes in.

Longevity through sirtuin stimulation

Sirtuins are longevity genes that help us get more energy for a longer period of time. Regular exercise stimulates this complex biochemistry giving us extra NAD+ for energy. Intermittent fasting also stimulates sirtuins, which adds to the extra energy and gives us longevity. This is not a bad deal when you look at it from a distance. We can achieve a lot preserving our energy through an active life style. Supplements can be an auxiliary measure, but they are not effective enough without positive lifestyle choices.

Nov
30
2019

Ketogenic Diet With Ketone Supplementation

There is a newer way to shed some pounds using a ketogenic diet with ketone supplementation. Ketosis with a ketogenic diet is difficult to achieve because it requires a lot of fat consumption and at the same time extremely low carb intake to trigger the ketogenic response. The October 2019 issue of LifeExtension magazine contained an article about a ketogenic diet with ketone supplementation. There are dip sticks with which you can test your urine for ketone bodies to verify that your metabolism has switched to ketosis. But you can also take some ketone supplements including beta-hydroxybutyrate. By adding this supplement it is easier to achieve ketosis.

Why do people think of starting a ketogenic diet?

Calorie restriction can mimic the effects of fasting. It leads to ketone production and improved energy metabolism. Your blood sugar goes down, you lose weight and diabetes becomes easier to manage. In an animal experiment with worms with the pretty name “C. elegans” researchers fed beta-hydroxybutyrate to these roundworms. They extended their lifespan by 20%.

Many who are motivated to go on a ketogenic diet hope to lose weight and others may hope to live longer. One large US study from the Brigham and Women’s Hospital, Boston, MA showed that mortality over a period of 25 years was lowest when carbohydrates were in the 50 to 55% range. In the same study when carbohydrates were replaced in ketogenic diets with animal-derived protein and fat sources, mortality increased by 18%. Meat and fat were from sources such as lamb, beef, pork, and chicken.

Problems with ketogenic diets

Physicians have had the concern that their patients on ketogenic diets tend to eat cheap fats and meats that contain trans fats. These unhealthy fats lead to premature death from accelerated hardening of the arteries resulting in heart attacks and strokes.

The alternative: a ketogenic diet with ketone supplementation

A new approach to anti-aging is taking ketone bodies like beta-hydroxybutyrate as a supplement. A publication from 2017 stated that oral ketone bodies could mimic the life extending properties of caloric restriction. The authors stated: “An exogenous ketone ester provides a new tool for mimicking the effects of caloric restriction that can be used in future research. The ability to power mitochondria in aged individuals that have limited ability to oxidize glucose metabolites due to pyruvate dehydrogenase inhibition suggests new lines of research for preventative measures and treatments for aging and aging-related disorders.”

Another publication from 2017 describes how ketones can be used as alternatives to glucose for energy. Brain cells and muscle cells in particular are very capable to utilize ketone bodies for energy. Two principal ketones are significant: acetoacetate and beta-hydroxybutyrate. The liver is involved when fatty acids are broken down and ketones are manufactured.

Ketone metabolism

Ketones provide energy without raising blood sugar levels or stimulating insulin secretion. The body requires less processing of ketones to release energy. This means that less NAD+ is used to metabolize ketones. The end result is that more NAD+ circulates in the body, which is used to repair damaged DNA and helps slow down the aging process. Ketones mimic many of the effects of caloric restriction and intermittent fasting dieting. Ketone metabolism reduces risk factors for diabetes and heart disease.

Human experiments

A 2018 study took 20 individuals aged between 18 and 35 years and tested them with an oral glucose tolerance test. Half of the subjects received a ketogenic hydroxybutyrate monoester, the other half just water (placebo group). The ketogenic group had 16% lower blood glucose levels. Their insulin sensitivity was 11% lower. The authors concluded: “These results suggest that ketone monoester supplements could have therapeutic potential in the management and prevention of metabolic diseases.”

Longevity in humans 

There has been a lot of research in the last few years indicating that sirtuins (SIR1 and SIR3) are important anti-aging genes. NAD+ needs to activate sirtuins first to make them effective. Unfortunately with the aging process less NAD+ is available, which leaves the sirtuins genes inactivated.

In rat experiments feeding of a ketogenic diet resulted in increased levels of NAD+. The researchers measured an oxidative DNA damage marker in the hippocampus of the brain. This showed much less DNA damage in rats fed a ketogenic diet when compared to controls on a regular diet.

Study of humans with Alzheimer’s disease

Another human study examined the blood of Alzheimer patients, patients with mild cognitive impairment and normal controls.  Alzheimer patients had low ketone levels in the blood as well as low 2-hydroxybutyric acid. Overall this showed that there is a change in metabolism in Alzheimer’s patients that leads to low ketone bodies in the blood on one hand and beta amyloid deposits on the other hand leading to memory loss.

A further experiment with Alzheimer’s patients showed that cognitive function improved after elevation of ketone blood levels following ingestion of beta-hydroxybutyrate.

A healthy way to raise ketones

Investigators in this human study determined whether various ketone-drinks were elevating blood ketone bodies reliably. 15 volunteers received ketone esters or ketone salts as a drink. There was a reduction of blood pH by 0.1 units using ketone esters. The ketone salts elevated the urinary pH from 5.7 to 8.5. An experiment with 16 volunteers measured the effect of having a meal before taking ketone esters. The ketone blood level showed a reduction of 33% after the volunteers consumed a meal and they took the ketone supplement afterwards. Ketone supplements lowered blood glucose, lowered free fatty acid and also lowered triglyceride concentrations. On the other hand, there was no change of the electrolyte levels. The authors said: “We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.”

Ketogenic Diet With Ketone Supplementation

Ketogenic Diet With Ketone Supplementation

Conclusion

The liver produces ketones when a person is fasting or is on a ketogenic diet. However the high fat content of a ketogenic diet can lead to atherosclerotic plaques in the arteries with the subsequent developments of strokes and heart attacks. A much safer way of raising ketone bodies in the blood is by taking ketogenic supplements by mouth. Animal experiments and clinical trials have shown that oral ingestion of ketogenic substances appear in the blood stream within 30 minutes and remain there for 3 to 4 hours. The body tolerates ketogenic supplements well with no side effects.

Prevention of Alzheimer’s disease, achieving weight loss and longevity

They likely will play a larger role in the prevention of Alzheimer’s disease in the future. Ketogenic supplements may be an adjunct to weight loss diets. In addition, fatty acids metabolize into ketones, which turn into energy in brain cells and muscles. Oral ketones stimulate the formation of NAD+, which activate longevity genes (sirtuins). Older people have a hard time to metabolize glucose because of certain enzyme deficiencies. But the brain and the muscle tissue can metabolize ketones rapidly, even in older age. Unfortunately the price of such supplementation is forbidding at the present time.

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Nov
24
2018

Intermittent Fasting May Benefit Health

There is a lot of discussion about the fact that intermittent fasting may benefit health. But there are a confusing variety of intermittent fasting schedules. This makes it difficult to compare notes regarding the specific effect of an intermittent fasting diet. Generally speaking when there is some form of calorie restriction, our body goes into a survival mode of operating. These types of diets provide enough nutrients to not get into malnutrition, but at the same time they may stimulate sirtuins, particularly SIR2. This is thought to be associated with longevity.

Various forms of fasting

Eating after 5 PM

The Taylors in the CNN article eat the same amount of calories, but they only eat after 5PM. They claim to have more energy and be less vulnerable to infections. They also think that they feel younger than in the past.

Fasting every other day

This was an observation in the 1980’s to help rats live longer compared to rats that have food available every day. Recent experiments on mice showed similar results: calorie restriction in whatever form leads to prolonged life and health.

Human fasting mimicking diet

A 2017 study on 100 humans divided this group into half. One half ate any food as they wished. The other half consumed only 800 to 1100 calories for 5 days of each month as a fasting mimicking diet. The experimental group had lower fasting blood sugars; cholesterol, triglycerides and other heart disease markers went down. The IGF-1 markers for various cancers also went down. The experimental group lost abdominal fat, but preserved lean body mass. Valter Longo, who co-authored the clinical study said that a human trial on longevity would almost be impossible to design, and would cost “a hundred million dollars or more. But if you look at the data from our trial … it would be hard to see how they would not live longer.”

5:2 diet

Patients are allowed to eat what they want for 5 days of the week, but then they restrict their diet for 2 consecutive days. The control group had no restriction of calories. The 5:2 experimental group had better glucose control and loss of abdominal fat than the control group.

Fasting can help you live-longer

Experts on calorie-restricted diets tell us that there is a switch in metabolism from burning glucose as fuel to using ketones as fuel. Extended periods of exercise will also cause a switch to using ketones as fuel. Repeated cycling from fasting to eating may also benefit our brain function. Intermittent fasting will help us cope better with stress and disease. But Dr. Longo says that this is only one aspect. He found in his research that with intermittent calorie restriction there is a multi-system regeneration going on. For instance, damaged white blood cells are depleted, stem cells are activated, blood sugar control is improved and heart risk factors are being controlled. Dr. Longo mentioned that when tissues are healthy and functional, risk factors for disease decrease.

Mechanisms behind longevity

Dr. Longo explained in detail the complex aging pathways that involve three components, IGF-1, mTOR and PKA. When lifestyle choices stimulate these genetic markers, accelerated aging is the consequence. But with the inhibition of those markers longevity will happen. Here are some of the effects on the body of a fasting mimicking diet.

  • Obesity diminishes, because of the weight loss effect due to missing calories.
  • Diabetes: insulin resistance becomes lower and blood sugar levels drop.
  • High blood pressure reduced: many patients were able to reduce their medications or discontinue them
  • Pain conditions improve as all kinds of pain disappears, an effect for which there is no explanation at this point
  • Autoimmune diseases like MS and rheumatoid arthritis improve, likely because of the effect of increased stem cell circulation
  • Prevention of heart attacks and strokes because of reduction of LDL, triglycerides and CRP
  • Cancer cure rates improve by protecting normal cells and the bone marrow
  • Longevity improved in mice with a 3-fold increase of their life span. Telomere length in humans was increased. Increased stem cells will find defective areas that need repair. This effect will open up a new chapter in medicine.
Intermittent Fasting May Benefit Health

Intermittent Fasting May Benefit Health

Conclusion

Calorie restriction is a powerful method to rejuvenate the body. Surprisingly 5 days out of one month of a calorie restricted fasting mimicking diet is all that is necessary to improve the body’s metabolism. Telomeres get increased, damaged white blood cells are removed and stem cells get stimulated. But weight loss, improvement of pain perception and cardiovascular risk reduction take place as well. In mice longevity was significantly prolonged, but this needs to still be shown in humans.

One can think of an intermittent fasting mimicking diet as a kind of internal cleansing. Following this it is easier to restart the metabolism with clean ingredients.

So far I have followed 11 courses of the fasting mimicking diet. But I don’t buy boxes of 300.00 USD every month. Instead I count calories myself, keep the diet balanced and buy the ingredients in the health food store. I agree that the fasting mimicking diet seems to be effective and it helps to keep my body mass index under control.