How L-Carnosine and Exercise May Block Glycation and Oxidative Damage Via Inhibition of Methylglyoxal

Researcher Alan R. Hipkiss of the University of Birmingham (United Kingdom) has proposed a theory explaining how L-carnosine inhibits glycation damage in aging humans and animals. He posits that one of the common mechanisms for increased sugar cross linking with proteins (glycation) is due to low NAD+ availability that causes an increase in compounds that cause glycation. NAD+ is important for the energy generation function of mitochondria. It can be formed in the body from sources such as tryptophan, aspartic acid, various forms of niacin including nicotinic acid and niacinamide. Low NAD+ can lead to accumulation of high levels of glycolytic triose phospates which break down into methylglyoxal. Methylglyoxal is known for its ability to cause glycation and oxidative damage to proteins and also for its involvement in mitochondrial dysfunction.

Hipkiss believes that L-carnosine reacts with methylglyoxal and renders it less able to trigger glycation and oxidation damage, thus explaining the many studies that have associated anti-aging effects such as reduced glycation, lower HbA1C measurements (a measure of glycated hemoglobin used to track long-term blood sugar levels), and oxidative damage with carnosine supplements. Carnosine tends to be concentrated in energy-intensive tissues such as the brain and skeletal muscles in which mitochondrial energy production is likely to result in higher ROS (reactive oxygen species) generation, thus the effects of carnosine are likely to be most pronounced in organs with higher metabolic activity.

The theory also explains how aerobic exercise acts counterintuitively to reduce oxidative damage. Exercise triggers higher metabolic activity that should at first glance result in even more production of ROS (reactive oxygen species) as mitochondria work to boost available energy to meet exercise demands. But as the mitochondria increase their activity, they recycle more NADH to NAD+ which causes lower levels of methylglyoxal, in turn reducing glycation and oxidative damage.

Carnosine Can Offer Some Benefits of Moderate Exercise

According to Hipkiss’s reasoning, it is plausible that carnosine supplements can provide an analogue to some of the important anti-aging effects of moderate exercise such as reduced damage from glycation, oxidation, and mitochondrial dysfunction. Such damage occurs more rapidly those suffering the ravages of old age, particularly those with age-accelerating diseases such as diabetes and neurodegenerative diseases such as Alzheimer’s Disease. As a result, carnosine supplements may be particularly helpful for older people who suffer from diabetes, neurodegenerative, and mitochondrial diseases because it is often difficult to get enough carnosine in the diet as most of the good sources of it are red meats such as beef that also tend to be high in artery-clogging fats.

Hipkiss does caution, however, that exercise appears to trigger additional benefits such as muscle cell reproduction possibly via increased ROS production and that carnosine by itself would not have the same effect. It’s interesting to note that some studies have found that high consumption of antioxidants may both simulate the antioxidant effects of moderate exercise while blunting the muscle-building effects.

Hipkiss also refers to related research showing that acetyl L-carnitine has many beneficial effects on increased energy production by mitochondria, ability to metabolize fats, and reduction of ROS generation. Carnitine supplementation, particularly along with alpha lipoic acid that greatly boosts its effectiveness, may be an ideal complement to carnosine supplementation. Learn more in L-Carnitine Helps Reduce LDL Cholesterol, Triglycerides, Blood Glucose, and Insulin in Fatty Liver Disease and Diabetes Patients.

Mixed Messages On Interaction of Exercise and Antioxidants

Strenuous exercise has been noted as causing oxidative damage to the body. Oxidative damage is one of the many culprits behind aging and disease. Thus there has been an interest in using high level of antioxidants to improve health.

A small number of studies show that supplementation with vitamin C and E (alpha tocopherol form) antioxidants may blunt exercise-induced improvements in insulin sensitivity. These studies found that people supplementing with these antioxidant vitamins did not experience improved insulin sensitivity from moderate exercise seen in exercisers who did not take antioxidant supplements.

ROS appear to be a sort of two-edged sword. They damage the body, causing damage to cell membranes, proteins, lipids, and more. But they also trigger repair and regeneration mechanisms to undo that damage or to grow new healthy cells to replace damaged old ones.

When ROS levels become very high, the rate of oxidative damage may outdo the repair ability of the triggered maintenance mechanisms. Conversely, greatly reducing ROS levels may avoid triggering those repair and regeneration mechanisms, perhaps because they seem unnecessary to the body.

It may be that antioxidants could be timed to shape overall ROS levels to optimize the overall effect on health. A person might consume extra antioxidants at a time selected to dampen damage from strenuous exercise. But other times, the person could take them at times apart from moderate exercise so as to allow moderate exercise to trigger ROS-initiated repair mechanisms and other benefits such as improved insulin sensitivity that might otherwise be suppressed.

Keep in mind that many other studies show that vitamin C and E help improve insulin sensitivity on their own, without exercise. There is clearly a lot of conflicting data and analysis as to the nature of the effects of antioxidants and exercise on common measurements of health.

It’s possible that many of these seemingly conflicting observations could be explained by some of the effects of antioxidants and exercise not being additive. Antioxidants can improve insulin sensitivity and reduce oxidative damage on their own in people who do not exercise much. Moderate exercise also reduces oxidative damage and improve insulin sensitivity. But it may be the effects simply are not additive under typical circumstances.

A mix of low ROS levels due to antioxidants combined with occasional spikes of higher ROS due to moderate exercise may be a way to achieve the best results from both. To achieve a full understanding, more research is needed to show both how to accomplish this and to demonstrate the actual effects in many people with different overall health conditions.

Consume Balanced Mix of Antioxidants from Foods and Supplements

As the understanding of antioxidants affecting exercise benefits is still poor today, certainly nobody should regard this conflicting information as a reason to avoid antioxidant rich foods or even using small to moderate quantities of a wide range of antioxidants. But it may be a sign that heavy supplementation of one or two antioxidants such as vitamin C and alpha tocopherol could reduce the benefits of exercise even though they do arguably help prevent certain kinds of oxidative damage in the body. For now, some good advice may be to get a wide mix of antioxidants from foods such as brightly colored fruits, green and leafy vegetables, and supplements while taking care to avoid unbalanced intake of any particular antioxidant.

Further Reading

Vegetarians May Suffer Shorter Life Due to Carnitine, Carnosine, and Vitamin B12 Deficiencies

L-Carnitine Helps Reduce LDL Cholesterol, Triglycerides, Blood Glucose, and Insulin in Fatty Liver Disease and Diabetes Patients

Carnosine: Exceeding Scientific Expectations

The Benefits of Carnitine and DHEA for Fat Metabolism

Aging, Proteotoxicity, Mitochondria, Glycation, NAD+ and Carnosine: Possible Inter-Relationships and Resolution of the Oxygen Paradox

On the enigma of carnosine’s anti-ageing actions

NAD(+) and metabolic regulation of age-related proteoxicity: A possible role for methylglyoxal?

Antioxidants prevent health-promoting effects of physical exercise in humans

Moderate exercise is an antioxidant: upregulation of antioxidant genes by training

Do Antioxidants Curb an Exercise Benefit? Study Shows Some Supplements May Affect the Impact of Exercise on Insulin Sensitivity

Do Antioxidants Limit Exercise Benefits?

Antioxidants Increase Insulin Sensitivity

A diet loaded with antioxidant rich foods improves insulin resistance

Antioxidant-rich diet improved insulin resistance

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