With so much evidence on the role nutrition plays on are-related disease and longevity, I often spend quite a bit of time researching different dietary protocols. As a neuroscientist, I am mainly interested in brain health, and indeed, several nutrients have demonstrated impressive neuroprotective anti-aging effect. Do these longevity foods and supplements hold the key to long and healthy life?
Well, turns out, how much we eat, or when we eat matters even more. And not just to our cognitive function. To our entire physiology.
In this overview, we’ll go over some of the most studied dietary modifications known to influence lifespan and healthspan: intermittent fasting, caloric restriction and the ketogenic (keto) diet. We will review what we have learned from recent evidence and how we can apply some of these insights in our daily lives. We’ll also cover some common mistakes I often see people make when implementing some of these methods.
Is eating less the key to longevity?
When scientists studied animals placed on different diets that restricted their caloric intake or mimicked fasting, they discovered that the duration and extent of the diets influenced lifespan and healthspan[1-4].
Now, this type of evidence makes many longevity researchers, myself included, very excited. But, also triggers some critical thinking. How does this apply to humans? Can we increase our lifespan and healthspan simply by eating less or, by eating less frequently? How this will affect our ability to live our life, think, feel, behave? Also, are there any long term side effects? Perhaps, we just wait until more data on humans will be available.
I don’t know about the waiting part. Kind of conflicting with the entire anti-aging idea. Perhaps, a good place to start, is to took into our history.
The evolution of Calorie restriction & intermittent fasting
Evolutionarily speaking, diets like intermittent fasting and calorie restriction were not “diets”. They were essentially a normal part of life. Simply put, our ancestors did not get too many options to choose from. Food was scarce and they had to survive.
As a result, our bodies (and other species as well) developed several mechanisms to deal with starvation. As a part of these, the body learned to retain energy stores that can be used later during times of food scarcity.
By now, your body has these intelligent survival mechanisms in place. It understands and knows how to deal properly with food scarcity and starvation. But, there is a problem. Times have changed. Food scarcity is not common anymore. In fact, for the first time in human history, we are dealing with the opposite problem. We are dealing with excessive caloric intake.
The body has evolved to store extra calories, and hasn’t learned yet how to deal with excessive caloric intake. It is no surprise then, that we see such a high rise in obesity, diabetes, and cardiovascular disease, not to mention age-related neurodegenerative diseases and memory deficits[5, 6, 7].
It’s a new world, and we are still evolving
This evolutionary shift from food scarcity to dietary excess, brings many challenges. For example, now, we have to learn when to stop eating, where in the past, it was rarely an option. Our ancestors simply ate what they could find. And in many cases, that was not a lot.
Clearly, we need to find a solution, as the modern eating habits are literally killing us. We can’t wait for evolution to catch up with these unhealthy habits either. Can fasting or calorie restriction help?
The data on calorie restriction and intermittent fasting is very encouraging, as many studies have shown they can decrease the risk for age-related diseases, and extend healthspan and lifespan.
These dietary restrictions mimc the same food scarcity we have evolved with. In fact, fasting and calorie restriction activate our ancient survival biological pathways that regulate energy levels, metabolism, and cell renewal/death. They can turn us from sick humans to fine tuned longevity machines.
Let’s look at fasting and calorie restriction in action.
The longevity fuel: From glucose to ketones
Metabolism is a complex biochemical process that combines calories with oxygen to release the energy your body needs to function. The body primarily uses glucose as its energy source. Most organs can store glucose as glycogen for later and use alternative energy sources such as fat and lactate when glucose is absent.
Our brain however, works differently:
- Glucose cannot be stored as glycogen in the brain and must be continually provided.
- The brain’s main alternative energy source is ketones.
Calorie restriction and fasting depletes the body’s glycogen storage. Eventually, there is not enough glucose present in the body overall, but also, not enough to meet your brain’s needs. The liver then breaks more fatty acids down into ketones, serving as an alternative energy source. You may have heard about this as being in a state of “ketosis”. It is the premise of the popular ketogenic diet, which will dive into later as well.
Here is some good news. As an energy source, ketones are very beneficial to our health. They have a higher energy capacity than glucose does when utilized by the body. Additionally, ketones have other health promoting actions. For example, ketones are neuroprotective in aging populations. Additionally, the ketone body beta-hydroxybutyrate has shown anti-inflammatory effect.
Fasting and calorie restriction benefits
Although both fasting and calorie restrictions have been extensively studied in animal models, much less studies have investigated their effects on a human population. Especially, with the necessary control groups to make conclusions from the study and long-term use.
With that said, overall, we can say that the evidence does suggest that fasting and calorie restriction:
- Modify the body’s stress response
- Increase the production of ketone bodies
- Regulate hormones related to hunger and fullness
- Optimize glucose and insulin signaling
- Reduce levels of inflammation.
- Increase neurotrophic factors that support the growth and survival of cells in the nervous system.
I want to pause here for a moment, and recognize that a big part of the anti-aging equation, is protecting our brains from the signs of aging. And this is where calorie restriction and intermittent fasting have shown some impressive neuroprotection benefits[6, 16]. In this process, brain cells are protected from environmental and genetic factors that lead to aging. Neuroprotection is important for preventing age-related brain disease and cognitive dysfunction.
Some of the cognitive effects of calorie restriction and intermittent fasting include:
- Boosts brain immune function.
- Enhances memory[10-12].
- Increases mental flexibility.
- Raises mood[13, 14].
- Improves motor coordination.
The ketogenic diet
While you may have heard about the ketogenic diet in terms of weight loss, it has shown promising anti-aging potential as well.
With the keto diet, you significantly reduce your sugars and carbohydrates intake and instead, eat more fats. Ideally, healthy fats. Due to the low levels of carbohydrates, the body cannot produce enough glucose to support the brain and other organs. The brain then must utilize other energy sources. This leads to the production of ketones for energy.
Now, the average American ingests approximately 55% of their calories from carbohydrates. In a ketogenic diet, carbohydrates are often reduced to 5-10% of the total calories, with 55-60% of the diet being fat and 30-35% protein. If your daily intake is 2000 calories per day, your carbohydrate intake would be as low as 20-50g for the keto diet.
With that said, a keto diet doesn’t mean zero carbs. This is important since you still want to provide your body with enough fiber to promote health gut microbiome. A few practical tips:
- Use “net carb” grams to calculate your carbs intake. Net carbs are the carbohydrates in foods that your body can utilize for energy. Simply subtract the grams of fiber from the total number of carbs.
- The total amount of net carbs can vary from one person to another. A good place to start may be 20 grams of net carbs per day, but some people can still be in ketosis with 50 grams or more.
- Ketone production can be enhanced further by increasing exercise in addition to fasting and/or calorie restriction. Timing also matters. For example, a fasted cardio session.
- Be mindful on your protein intake. The body can still convert protein to glucose (a process called gluconeogenesis), and theoretically, can kick you out of ketosis.
- Do you find the keto diet too strict? try to combine a lower carb approach (but not keto) with intermittent fasting. You may still activate the longevity pathways and other protective mechanisms including ketosis. I find this approach much more practical to continue long-term.
Intermittent fasting vs. calorie restriction, practical insights
While we still need more data on humans, it seems that the combination of mild calorie restriction and intermittent fasting may be the most beneficial, especially in combination with some form of a keto or low carb approach. Looking at the evidence including anecdotal, here are some useful tips to consider:
- Humans are not mice. It is difficult to significantly restrict calories. Let’s face it, dieting, in general, is HARD! Restricting calories long term with all these foods around us all day can be a very hard thing to do. With that said, mild calorie restriction is quite possible, especially when combined with fasting.
- Long term calorie restriction may increase the risk of nutritional deficiencies or eating disorders.
- Intermittent fasting is probably the most practical and easiest to implement. One meal a day has become a popular method for that reason. Especially when combined with a low-carb approach. When your body runs on ketones, you are significantly less hungry.
- Fasting doesn’t mean that you can eat whatever you want during your feeding windows. Eat healthy! (See next sections for more diet tips).
- Both calorie restriction and fasting are more about health and longevity than weight loss. While they seem like an easy way to lose weight short term, many people often struggle keeping the weight off once they discontinue and go back to the way they used to eat.
- Test for nutritional deficiencies. Rather than guessing, have your doctor test your levels and address any gaps with foods and supplements.
Dietary tips for longevity
The ideal approach may be very different from one person to another. Your health, nutritional status, objectives, preferences, lifestyle, and many other factors all matter and should be considered. Although there’s no magic formula that works best for everyone, most people can benefit from the following general guidelines:
Eat high-quality whole foods
Focus on natural high-quality whole foods and avoid processed foods, artificial sweeteners, and foods high in sugars. Be mindful about packaged foods, as they are often loaded with unhealthy and even toxic ingredients.
Consider Mediterranean inspired eating
This eating pattern has been well known for its health benefits and longevity. This diet is mainly plant-based, with:
- Plenty of fresh fruits, vegetables, and leafy greens, nuts
- Healthy fats from raw nuts, seeds, olive oil and avocados
- Plant proteins such as beans and legumes
- Moderate amount of wild fish and high quality meat.
- Processed foods are minimized, with a focus on plant-based whole foods instead.
Gut health matters
Your gut health has extensive effects on your entire health including longevity. This area has recently been a primary focus in research, finding that immune function, mental health, and physical health can all be modulated by our gut microbiome. Make sure to include plenty of fiber from whole foods, especially leafy green and non starchy vegetables.
Several natural ingredients have shown to activate the same longevity pathways that are activated during fasting and calorie restriction. They are known as as calorie restriction mimetics. Some of these includes NAD+ precursors, spermidine, resveratrol, curcumin, green tea extract (EGCG), and quercetin. These can be used to mimic some of the benefits of calorie restriction, but can also augment your fast.
Side effects & risks
I find that moderation and common sense goes a long way. It’s important to be mindful and not get carried away with some of these popular health trends we all read online. Longevity is a marathon, not a sprint. Safety and thinking long terms are key. This is why it is important to first speak with your doctor and run some tests if needed. Also, as I mentioned, do not implement sudden, substantial dietary changes that your body may not be ready or able to handle.
Some of the main risks include:
- Calorie restriction. Be careful not to reduce your calories too low, and test your essential nutrients levels. Some of the risk of long term calorie restriction include: nutritional deficiencies, reduced production of sex hormones, and osteoporosis, especially in females.
- Keto Diet. Common adverse effects known as the “keto flu” may occur initially as it takes time for your body to adjust. Symptoms include fatigue, dizziness, “brain fog”, vomiting, insomnia, and constipation. However, make sure to keep hydrated and replace electrolytes can help reduce the risk of these short-term symptoms. The ketogenic diet is not recommended for those with pancreatitis, fat metabolism disorders, liver failure, and diabetes, due to the increased risk of ketoacidosis.
Other lifestyle habits that promote longevity
The evidence on each of the following lifestyle traits is absolutely incredible showing a positive influence on health, wellness, quality of life, and longevity.
- Stress levels
- Exercise, movement and activity level
- Your emotional state and level of optimism
Try to be mindful of these in your life, and don’t get discouraged if you experience challenges with some of these. Keep in mind, a health and wellness longevity plan is never about perfection, it’s about balance.
Whether for brain health, longevity, or weight loss, dieting can be difficult and discouraging, especially when you don’t see results. Keep that in mind, just like many medications, at least a month of practice is needed before starting to see or feel some of the benefits.
Aside from research, there are tons of anecdotal evidence from friends and family we can pull from. Ask your friends and family whether they have tried these diets, their experience, what worked for them, and what didn’t. This doesn’t mean what worked for them is going to work for you, but there’s still a lot we can learn from their experiences.
For example, when my mom began the ketogenic diet, she only did it for weight loss, but she has found numerous additional benefits! She tells me all of the time how removing artificial sugars and reducing her carbohydrate intake have made her feel more energetic and helped reduce injury-related inflammation.
Also, feel free to modify the diet if you find it too strict, and still see benefits. It’s not about perfection, it’s about finding your own individual balance. Overall, eating healthier is something we should all strive for to improve our healthspans and lifespans. Based on what we have learned, it seems that practices like fasting, mild calorie restrictions and a lower carb approach may help you get there.