Life Extension Magazine®

Issue: Oct 2019

Healthy Way to Benefit from Ketones

The low carb/high fat ketogenic diet has become a popular way to lose weight. But ingesting bad fats increases cardiovascular risks. Scientists have identified a healthy method to increase ketones without the difficulties of a ketogenic diet.

By Chuck Rossner

Lately it seems like everyone’s trying ketogenic diets to lose weight.

Ketones are compounds normally produced in the body during times of fasting. They provide easy-to-use energy to the brain and muscles.

Ketones have been linked to longevity in animal models, and to improved metabolism in humans and animals.1-8

By severely limiting carbohydrate intake, we can mimic some of the metabolic effects of fasting, leading to increased production of ketones.

Studies have shown that carbohydrate restriction can lead to improved energy metabolism, reduced blood sugar, weight loss, and more. In one animal study, increasing ketone blood levels extended the average lifespan by approximately 20%.1

But many doctors warn against trying ketogenic diets. For one, they’re notoriously difficult to maintain. And they often require people to increase their intake of unhealthy fats.

As a result, some of these diets have been tied to higher risk for cardiovascular disease and overall increased risk of premature death.9-11

Scientists have identified a potential solution. They’ve found a way to safely raise blood levels of ketones—and even enhance the body’s ability to produce its own ketones—without resorting to harmful high-fat diets.

What Are Ketones?

Woman holding kale

Glucose, largely derived from carbohydrates, is the standard energy source for most cells.

In times of prolonged fasting, when glucose is low, the liver is forced to produce an alternative fuel source, ketones, which it makes from stored fats.

Science has found that ketones offer advantages over glucose. They’re more energy efficient12 and are effective energy sources for tissues with high metabolic rates like the brain and muscles.

Even more important, they’ve been linked to increased longevity in animal models and improved metabolism in human and animal studies.1-8

Two of the principal ketones are acetoacetate and beta-hydroxybutyrate (BHB). These compounds can be broken down by cells to provide energy.

BHB, created from fatty acids in the liver, not only regulates energy expenditure, it also helps modulate metabolism.

Ketones are superior to other fuel sources for two main reasons:1,2,4,8

1. Unlike carbohydrates, ketones do not raise blood glucose levels and do not stimulate insulin secretion.

2. Ketones require less processing than glucose to harness their energy. That means they consume less NAD+ in their metabolism, leaving more of it circulating in the body.13 NAD+ helps repair damaged DNA, and slow certain aging processes.

Ketones aren’t just an alternative fuel source. They change our metabolism, mimicking many of the beneficial effects of caloric restriction, and intermittent-fasting diets. That reduces risk factors for metabolic disease, diabetes, and cardiovascular disease.3,4

In addition, ketones have recently been discovered to be important signaling compounds, activating longevity pathways that protect cells from age-related damage and deterioration.1,2,5-8

Man clutching his heart

What You Need to Know

Boost Ketones Without a Risky Diet

  • Ketones are compounds produced by the liver during times of fasting or extremely low carbohydrate intake.
  • Ketones are used as an alternative fuel by the brain and muscles. They also activate pathways linked to lifespan and health-span extension.
  • The ketogenic diet stimulates ketone production but requires extremely high fat intake that has harmful health consequences.
  • Safer alternatives directly supply ketones that can be absorbed and used by the body. Beta-hydroxybutyrate regulates energy expenditure and helps modulate metabolism. Mangiferin and a resistant starch also boost the body’s ability to make its own ketones.
  • It is now possible to obtain the benefits of ketones without the difficulties and downsides associated with prolonged fasting or the ketogenic diet.

Increased Longevity

senior man stretching in a park before a job

Ketones provide life-extending effects similar to those attributable to caloric restriction and fasting,1,2,8,14 including maintaining protective levels of NAD+ in cells.

NAD+ is critical for vital cellular processes. Sirtuins are proteins in cells that have lifespan-extending properties. Sirtuins require NAD+ to function properly.

In animal studies, increasing ketone levels in the body leads to higher levels of NAD+ and a boost in sirtuin function.2 This reduces damage to DNA, which is associated with age-related disease and dysfunction.

For example, in one study1 of the roundworm C. elegans, a common model organism for research on longevity, supplementing its diet with the ketone beta-hydroxybutyrate increased the average lifespan by approximately 20%.

This effect has also been shown in mammals. In aging mice, diets that boost blood ketone levels extend lifespan by approximately 14%.7 Even more importantly, ketones prolong healthy life, or healthspan.7,14

Improved Metabolic and Physical Health

Using ketones as an energy source improves our metabolism, reducing risk factors for cardiovascular disease, diabetes, and other conditions. It also provides a potent fuel to muscles to enhance physical fitness.

In one study, rats were fed a diet in which 30% of calories were derived from ketones.3 This caused a reduction in cholesterol and triglyceride levels.

The rats also showed a boost in physical ability: They ran an average of 32% farther on a treadmill than rats fed a regular diet over a five-day period.

The metabolic benefits of ketones have been demonstrated in humans as well.

A study recently published in The Journal of Physiology found that healthy, young adults given a ketone supplement showed improvements in metabolism during an oral glucose tolerance test.4 After ketone supplementation, beta-hydroxybutyrate levels went up, total blood glucose elevation during the oral glucose tolerance test was lower, fatty acid levels decreased, and insulin sensitivity improved by about 11%.

These findings suggest that acute ketone supplementation may improve markers of metabolic response to an oral glucose load.

A Boost in Brain Health

Ketones are easily used by the brain as a fuel source. Not only can this improve brain function, it can also have a neuroprotective effect, shielding against age-related cognitive decline.

In roundworms, the ketone beta-hydroxybutyrate helps protect against the harmful effects of two abnormal proteins that contribute to the development of Alzheimer’s and Parkinson’s disease.1

In aging mice, memory and other cognitive functions are preserved and improved through dietary enhancement with ketones.3,7,14

This link between ketones and brain function carries over to humans. People with Alzheimer’s disease, the most common form of dementia, tend to have lower blood levels of ketones.15

In people with cognitive dysfunction, the brain’s ability to use glucose as a fuel appears to be impaired.

A study published in The Neurobiology of Aging explored whether raising blood levels of the ketone beta-hydroxybutyrate, an alternative fuel, could improve their brain function.16

Subjects with Alzheimer’s or mild cognitive impairment, a common precursor to Alzheimer’s, were given a supplement drink that raised blood ketone levels. The increase in ketones in most study subjects correlated with improvements in cognitive function, particularly memory.16

Issues with the Ketogenic Diet

One way to raise ketone levels is by forcing the body to create more of them. That’s the goal of the popular ketogenic diet. Severely restricting carbohydrate intake and replacing those calories with a large amount of fat makes the liver pump out ketones.

But there are several downsides to this strategy:

  • Eliminating carbs means dramatically reducing intake of fruits, vegetables, and whole grains. These foods are a source of dietary fiber, which is critical for digestive health. Insufficient fiber has been linked to gastrointestinal disorders and colorectal cancer.17,18

  • Very low carbohydrate intake has been linked to premature mortality.11

  • A high-fat diet can cause elevated triglycerides, other lipid abnormalities, and detrimental metabolic changes, all risk factors for cardiovascular disease.10,19

  • In people on a ketogenic diet, the risk of atherosclerotic plaque development in arteries, which often leads to cardiovascular disease, may be increased.9

  • High-fat, low-carb diets can negate or even reverse the brain benefits of ketones, leading to deterioration in attention, processing speed, and mood.10

In other words, the potential problems of the ketogenic diet may outweigh the benefits. It is not recommended for people unless they have a specific medical condition for which it is indicated.

Raise Ketones the Healthy Way

Scientists recently set out to create a healthier way to raise ketone levels without the risks of the ketogenic diet or prolonged fasting.

They accomplished this by combining the ketone beta-hydroxybutyrate with two other nutrients that aid in the body’s ketone production.

When ingested orally, beta-hydroxybutyrate is easily absorbed into the bloodstream, providing the same benefits as ketones produced by the liver. Beta-hydroxybutyrate can increase blood levels to the range typically induced by a ketogenic diet.20

Mangiferin is a compound found in plants, especially mangos—hence the name. It has been shown to help spur the production of more ketones by the body.

In one randomized trial, researchers demonstrated that 150 mg of mangiferin per day significantly increased blood levels of ketones, presumably by stimulating the liver to boost production of them.21

In response to mangiferin supplementation, beta-hydroxybutyrate increased by about 18% and acetoacetate levels increased by approximately 10%.

A resistant starch, like cassava, is a complex carbohydrate that is not efficiently broken down by our digestive enzymes.22

Benefits of “Resistant Starch”

Other forms of starch are broken down into simpler carbohydrates, which raise blood sugar levels after a meal, triggering insulin secretion.

Because they are not digested rapidly by humans, resistant starches do not raise blood glucose or cause an insulin response.

Besides being a source of fiber, resistant starches have several other beneficial effects. They help support healthy gut bacterial growth, promote a feeling of fullness, increase insulin sensitivity, and preserve lean body mass.23

Resistant starches also enhance the body’s production of butyrate, which is used to make more ketones, and to stimulate many of the same longevity-promoting pathways as ketones.5,24,25

Summary

senior couple out for a jog

Ketones are an alternative fuel for our cells, with several advantages over glucose.

Normally produced by the liver during fasting, ketones are quicker and easier to metabolize than glucose and provide a potent energy source for the brain and muscles.

They also activate pathways tied to improved healthspan and longevity.

The most popular ways to increase production of ketones are by prolonged fasting or the ketogenic diet. High fat ketogenic diets, however, are potentially dangerous, negating the benefits of the increased ketones.

Scientists have now developed a safer alternative that directly supplies beneficial ketones and boosts the body’s ability to produce ketones. It does so without the harmful effects of ketogenic diets.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Edwards C, Canfield J, Copes N, et al. D-beta-hydroxybutyrate extends lifespan in C. elegans. Aging (Albany NY). 2014 Aug;6(8):621-44.
  2. Elamin M, Ruskin DN, Masino SA, et al. Ketogenic Diet Modulates NAD(+)-Dependent Enzymes and Reduces DNA Damage in Hippocampus. Front Cell Neurosci. 2018;12:263.
  3. Murray AJ, Knight NS, Cole MA, et al. Novel ketone diet enhances physical and cognitive performance. FASEB J. 2016 Dec;30(12):4021-32.
  4. Myette-Cote E, Neudorf H, Rafiei H, et al. Prior ingestion of exogenous ketone monoester attenuates the glycaemic response to an oral glucose tolerance test in healthy young individuals. J Physiol. 2018 Apr 15;596(8):1385-95.
  5. Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014 Jan;25(1):42-52.
  6. Newman JC, Verdin E. beta-hydroxybutyrate: much more than a metabolite. Diabetes Res Clin Pract. 2014 Nov;106(2):173-81.
  7. Roberts MN, Wallace MA, Tomilov AA, et al. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metab. 2017 Sep 5;26(3):539-46 e5.
  8. Veech RL, Bradshaw PC, Clarke K, et al. Ketone bodies mimic the life span extending properties of caloric restriction. IUBMB Life. 2017 May;69(5):305-14.
  9. Azevedo de Lima P, Baldini Prudencio M, Murakami DK, et al. Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy. Nutrition. 2017 Jan;33:271-7.
  10. Holloway CJ, Cochlin LE, Emmanuel Y, et al. A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects. Am J Clin Nutr. 2011 Apr;93(4):748-55.
  11. Seidelmann SB, Claggett B, Cheng S, et al. Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet Public Health. 2018 Sep;3(9):e419-e28.
  12. Puchalska P, Crawford PA. Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. Cell Metabolism. 2017;25(2):262-84.
  13. Elamin M, Ruskin DN, Masino SA, et al. Ketone-Based Metabolic Therapy: Is Increased NAD(+) a Primary Mechanism? Frontiers in Molecular Neuroscience. 2017;10:377-.
  14. Newman JC, Covarrubias AJ, Zhao M, et al. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice. Cell Metab. 2017 Sep 5;26(3):547-57 e8.
  15. Ciavardelli D, Piras F, Consalvo A, et al. Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer’s disease subjects. Neurobiol Aging. 2016 Jul;43:1-12.
  16. Reger MA, Henderson ST, Hale C, et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging. 2004 Mar;25(3):311-4.
  17. Encarnacao JC, Abrantes AM, Pires AS, et al. Revisit dietary fiber on colorectal cancer: butyrate and its role on prevention and treatment. Cancer Metastasis Rev. 2015 Sep;34(3):465-78.
  18. Kunzmann AT, Coleman HG, Huang WY, et al. Dietary fiber intake and risk of colorectal cancer and incident and recurrent adenoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr. 2015 Oct;102(4):881-90.
  19. Kosinski C, Jornayvaz FR. Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies. Nutrients. 2017 May 19;9(5).
  20. Stubbs BJ, Cox PJ, Evans RD, et al. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017;8:848.
  21. Na L, Zhang Q, Jiang S, et al. Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial. Sci Rep. 2015 May 19;5:10344.
  22. Lehmann U, Robin R. Slowly digestible starch - its structure and health implications: a review. Trends in Food Science & Technology. 2007;18:346-55.
  23. Higgins JA. Resistant starch and energy balance: impact on weight loss and maintenance. Crit Rev Food Sci Nutr. 2014;54(9):1158-66.
  24. McNabney SM, Henagan TM. Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance. Nutrients. 2017 Dec 12;9(12).
  25. St-Pierre V, Courchesne-Loyer A, Vandenberghe C, et al. Butyrate is more ketogenic than leucine or octanoate-monoacylglycerol in healthy adult humans. Journal of Functional Foods. 2017/05/01/;32:170-5.

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