Professor David Sinclair is arguably the smartest and perhaps the most well-known personality in the field of anti-aging research.  I have been fascinated by his work over recent years.  

Sinclair has been involved in a lot of cutting-edge research in the anti-aging field over the past few decades and has a deep understanding of DNA and molecular biology.  

I recently listened to his new book Lifespan: Why We Age – and Why We Don’t Have To, and it triggered a range of thoughts around calorie restriction and nutrition, both positive and negative, that I wanted to share.

Overconsumption is the cornerstone to many of the modern diseases of aging.  However, the fundamental flaw in Sinclair’s argument (and many others who give similar advice) is that we can’t simply apply theories developed with yeast cells in a petri dish or lab rats (where food inputs are externally controlled) to free-living humans who can buy whatever they want whenever they want.

Some stress is good

Before I get into my disagreements with Professor Sinclair, let me outline some of the things he highlights that he discusses that I agree with.

Firstly, nature is cyclic.  We have:

• day/night
• hot/cold
• dry/wet
• summer/winter
• feasting/fasting.

It is these periods away from the average that have forced everything in nature (including us) to adapt to be less fragile.  

These swings away from status who are akin to resistance training for our metabolism.  Without some oscillation, we become limp and weak at one extreme or the other (i.e. either obesity or frailty).   

While we need enough energy and nutrients (including amino acids) to survive and thrive, times of occasional scarcity help us clean our house and repair to ensure we are primed for future growth and a long and healthy life.  

Sinclair highlights that our inbuilt repair systems kick in during periods of low energy availability.  When we have less food available, our bodies turn to our stored energy (i.e. glucose in our liver, muscle and blood, fat on our bum and belly and eventually our muscles and organs).  

Like a bushfire before the wet season, Sirtuin proteins go to work when we have less energy coming in, cleaning out the old and decaying parts of our body and making everything ready for new growth when the good times return.  

Sinclair has also been instrumental in pioneering a deeper understanding of the action of NAD+ (a downstream metabolite of niacin or vitamin B3 and the amino acid tryptophan) which resets many things to a more youthful state.  The image below shows the essential nutrients that your body uses to make NAD+ (i.e. niacin and tryptophan, with magnesium, thiamine and B6 as cofactors).  

Much of Professor Sinclair’s recent work has focused on synthesising and commercialising NMN (nicotinic acid mononucleotide), which is an immediate precursor to NAD+ in our body.  

Later in this article, we’ll come back to how you can optimise your diet to improve your NAD+ levels without relying on high-priced ‘quick fix’ supplements.  

The contrast between the foods that contain the essential nutrients required to make NAD+ naturally (i.e. niacin and tryptophan, with magnesium, thiamine and B6 as cofactors) and Sinclair’s nutritional recommendations might surprise you.  

The bottom line is that you will probably need to supplement with NAD+ if you do follow his recommendations because you won’t have enough of the essential substrates to make enough of it yourself.  

You can get too much of a good thing

In Lifespan, Sinclair describes his early research into the life-extending effect of calorie restriction on yeast and mice.  

Yeast cells live only a few weeks, so it’s easy to see how feeding them more or fewer calories affects their lifespan.

Mice are a little closer to humans.  They only live a few years, so you can feed them with controlled portions of different foods and study how they respond.  

Sinclair observed that yeast and mice undergo less metabolic stress when they are fed less.  Excess growth can lead to more rapid aging, including the growth of cancerous cells, which have a constant source of fuel and no periods of restricted energy.

To date, there have been two experiments on monkeys in captivity (as primates, they are much closer to humans) where they tried to restrict energy intake.  In one study, the monkeys were fed more or less of their natural diet, while in the other study, the monkeys were fed more or less of a more processed refined food.  

But unfortunately, the results didn’t provide clear outcomes that might give us insights into healthy human longevity.  When the monkeys ate less of their natural diet, they saw no benefit from the calorie restriction. However, monkeys fed less processed food seemed to do much better (note: the monkey on the right looks younger than the monkey on the left even though they are the same age). 

It seems that energy restriction may only be beneficial because you’re eating less processed, damaging, nutrient-poor inflammatory foods.  However, if you’re consuming a nutritious diet, chronic calorie restriction doesn’t seem to add any benefit.  

In fact, our satiety analysis suggests that consuming a nutrient-dense diet tends to align with an adequate (but not excessive) energy intake without having to work too hard to restrict.  When you make better food choices, you don’t need to worry so much about how much you are eating.

Calorie restriction in humans

Sinclair also profiles members of the Calorie Restriction Society who intentionally restrict their energy intake to about 75% of maintenance calories in an attempt to live longer and healthier lives.  

He describes meeting with CR Society Board members Paul McGlothin Meredith Averill (pictured below).  Even though their blood markers look better, he notes that they always wear jumpers because they are perpetually cold and look quite wrinkled for their age.  

In the 90s, there was a Calorie Restriction with Optimal Nutrition movement led by Roy Walford after he emerged from the Biosphere 2 experiment.  

Walford’s goal was to design nutrient-dense recipes that would enable people to get adequate nutrition with fewer calories (i.e. calorie restriction without malnutrition).

A lot of my early thinking around Optimising Nutrition came from studying what Walford was trying to do.  It was certainly a worthwhile quest to find foods that would provide adequate nutrients without excess energy.  However, I was disappointed when I analysed the meals he recommended and discovered that they were not particularly nutritious in terms of all the essential micronutrients per calorie!  

Fun fact:  The “CRON” in Cronometer comes from the Calorie Restriction with Optimal Nutrition. 

Sadly, Walford died in 2004 at the not-so-ripe age of 79 of complications related to ALS (an autoimmune disease).  Interest in calorie restriction has dwindled since then. 

Without any meaningful controlled studies on the effects of intentionally restricting calories, we don’t know much about the life-extension benefits of extreme calorie restriction in humans.   

To summarise, a crude summary of Sinclair’s chapter on calorie restriction and nutrition goes something along the lines of 

It seems beneficial to restrict calories to live longer, but it’s hard to do and the people who are trying to do it don’t look very flashy.  

If you want to have a crack at changing your diet and lifestyle, you could try to eat less protein (especially meat and dairy) and perhaps try some intermittent fasting which appears to be good, but not really that easy.  

But, if you don’t want to make a change, let me tell you about all my research that I’m trying to commercialise once I prove it works in humans.  

Alternatively, I could just sell you my dream, and you’ll buy it anyway, regardless of the lack of human research.

What we do know for sure

Optimising involves finding the balance point between extremes.  Context is critical, but it’s not sexy. But if you want to extend your lifespan and lose fat (and not just weight from your wallet), it’s important to pay attention to the nuance.   

What we do know about weight loss is that it is hard for people to do in our modern food environment and very few people succeed in the long term.  

The people that tend to do best in managing their calorie intake to optimise their health are the bodybuilders who use apps like Cronometer and MyFitnessPal to control their calorie intake and ensure they are getting enough protein to maintain their precious muscles and manage satiety.  

Rather than extreme restriction or continual starvation (you don’t need to look like a fitness model or a board member of the Calorie Restriction Society), we do know that it is critical to maintain a healthy body composition that tends to align with healthy fertility.  

With some basic measurements and tools, you can guide your nutritional and metabolic ship with small refinements towards nutritional optimisation, healthy body composition and longevity.  

Waist-to-height ratio

Maintaining a waist-to-height ratio of around 0.5 tends to align with optimal longevity in adult humans.  

While being overfat is not ideal, being underweight is also not optimal and can lead to reduced immune function, depression and other conditions related to malnutrition.

HBA1c

Maintaining a healthy HbA1c (i.e. a three-month average of your blood sugar) also aligns with a lower risk of mortality from stroke, heart disease, and dying of any cause.  

Having a lower HBA1c also decreases your chances of getting cancer.  

Body fat

When it comes to managing your blood sugar, the bottom line is that you need to reduce your carbs and fat intake to maintain a healthy level of body fat and stay within your personal fat threshold.

Fertility, attractiveness and overall health tend to align with a healthy body mass index.   

IGF-1

Another factor that is often talked about in anti-aging circles is insulin-like growth factor (IGF-1).  As you can see from the chart below, there is a ‘sweet spot’ for IGF-1.  

At one extreme, we end up with too much growth (which leads to obesity and cancer) and at the other, we have too little IGF-1 (which leads to sarcopenia and frailty).  

mTOR

The same is true for mTOR (mammalian target of rapamycin).  mTOR stimulates growth, but too much growth can be problematic.  Taking exogenous insulin or steroids to get as big and strong as possible is not necessarily metabolically optimal.

Lean muscle mass

However, there is no need to be bigger or stronger at all costs; we do know that having a higher fat-free mass index aligns with greater longevity (Genton et al., 2013).   More muscle aligns strongly with more resilience as we age.  

We tend to lose muscle mass at a rate of 3 to 5% per decade after about 30 and eventually suffer from sarcopenia (i.e. excessive loss of muscle).  It is for this reason that the recommended protein intake for older people increases with age to ensure that excessive loss of lean mass is avoided.  Older people tend to have a lower appetite and are less likely to undertake any resistance exercise to build muscle. Hence, dietary protein becomes more important. 

Sadly, many older people find their health quickly deteriorates after they have a fall or break their hip, and they never fully recover.   Hip fractures tend to be more common in older vegan and vegetarian people who are consuming a lower protein diet due to a lower bone mineral density.  Several studies have shown that the all-cause mortality rate doubles for elderly patients after a hip fracture.  Often, they die not too long after their fall from complications from surgery, medications or other conditions, such as pneumonia, that they catch during their hospital stay.  

Regardless of how it happens, your health span is likely to diminish rapidly once you lose your mobility, independence, and the ability to feed yourself and wipe your own bum.  

Once you are dependent on someone else for your food, showering and toileting, your quality of life and nutrition is out of your control and you have the potential to go into free fall as you become part of the aged care system that is highly commercialised and optimised for profit, not necessarily your health, happiness or optimal nutrition.  

Maintaining a healthy body composition (i.e. more muscle and less fat) will give you better odds of living a long and healthy life and extending your health span.  In my mind, this is a much safer bet than putting your hope in protein restriction based on observations in yeast cells and mice in captivity who could not tell the researchers how perpetually cold, miserable and depressed they felt while being fed less food than they would have liked.

Is “too much protein” harmful?

Where my views become diametrically opposed to Sinclair’s hypothesis is when he starts talking about limiting protein (particularly animal proteins).  This is a nuanced topic that I don’t see many people addressing, so I’ll do my best to explain it.  

Sinclair seems to align with the work of the likes of Dr Valter Longo and other plant-based longevity researchers who seem to start from the position that protein, particularly from animal sources, is implicitly bad. 

MORE protein is not necessarily better

It’s important to note that simply eating more protein is not a smart play.  The satiety analysis chart below from forty thousand days of data from Optimisers shows that simply eating more protein (without regard to the easy energy from fat and carbs) will lead to greater overall energy intake (see Why does protein suppress your appetite?).  

A higher percentage of protein is important!!!

It’s important to be clear about how we quantify our protein intake.  

When we look at protein in percentage terms it tells a very different story.  A higher percentage of energy from protein has a strongly positive impact on satiety.  

It is widely recognised that protein is the most satiating macronutrient and our satiety analysis aligns with the Protein Leverage Hypothesis which suggests that, in a free-living environment, we continue to consume more food until we get the protein we need to maintain a healthy lean mass.  

The percentage of energy from protein is the single strongest determinant of satiety (i.e. under-eating or overeating).  Due to the massive satiety effect, it is very hard to overeat protein in the absence of energy from refined carbs and/or fat.

Manage your intake of easy energy

It’s not a matter of eating more protein, but rather consuming less easy energy from processed fats and carbs sources.  

Unfortunately, we have optimised our modern food environment for hyper-palatability with an abundance of easy energy from fat and carbs with less protein (which tends to be more expensive).  

A growing number of us have more than enough stored energy and need to find a way to manipulate our diet to reduce calorie intake without having to suffer through unbearable hunger.  

You are not a yeast cell living in a petri dish or a mouse living in a cage being fed limited rations by some external deity.  You have free choice and a 7-Eleven on every corner where you can buy cheap processed food to give you easy energy at any time of the day.  

More often than not, we eat until we are no longer hungry.  Hence, to optimise body composition, avoid modern diseases, optimise your metabolic health and increase your chances of living a longer, independent and happy life, you need to find a way to manage your appetite so you are able to eat less without constant external restriction.  

What about fasting?

Sinclair also espouses the benefits of fasting or time-restricted eating.  

Fasting can be a double-edged sword.  There are undoubtedly benefits of having a hard stop to your eating window to limit your calorie intake.  There is also no need to eat if you are not hungry. When you do eat, it seems that it is beneficial to front-load your protein intake to maximise your satiety.

However, similar to calorie restriction, fasting relies on your limited willpower and constantly fighting against your appetite.  Without attention to food quality (i.e. satiety and nutrient density), you are more than likely to eat a whole lot more food when you do eat, and that food you eat when you are starving is likely to have a lower nutrient density and lower satiety value (so there is every chance you will eat more overall, in spite of your self-deprivation).  

So, while limiting your eating window has benefits, those benefits will be limited if you don’t pay attention to food quality (i.e., nutrient density).  

Is “plant-based” the solution?

Sinclair’s foundational premise of Lifespan is basically, “calorie restriction is good, but we all suck at it, so here are a bunch of other things that we’ve been working on that you can buy in a bottle that we think might give you similar benefits.  My father takes them, and he’s doing pretty well. So maybe you should, too?”  

In his chapter entitled What You Can Do Now, he recommends minimising protein, particularly meat and dairy.  He parrots the line that animal-based proteins have a different amino acid profile and can be dangerous.  

However, it’s not the amino acid profile of plants vs animal proteins that is the issue (see Are All Proteins Created Equal?).  As we saw above, we tend to eat less when our diet consists of a greater percentage of protein.  Our extensive data analysis and a whole pile of other research demonstrate that actively avoiding protein is perhaps the dumbest thing you can do if your goal is to avoid overeating.  

Due to protein density (i.e. protein per calorie and protein per weight of food) and bioavailability (the amount of protein your body absorbs from a food), you will have to consume a LOT more calories to get the protein you require if you eat only plant-based foods. 

As discussed in “What Would Happen If We All Went Plant-Based“, avoidance of the most efficient protein sources is likely to lead to an increase in calorie intake while obtaining significantly fewer essential nutrients and, hence, poorer health outcomes.  This overconsumption is bad not only for your metabolic health but also for the planet.  

You need to find a way to get enough nutrients without excess energy

As I mentioned above, Roy Walford’s dream of optimising for more of the essential nutrients with less energy is a very worthy goal.  Over the past four years, we’ve worked pretty hard to crack the code.  

More recently, we’ve been working on making nutrient density more accessible by creating a range of recipe books optimised for maximum nutrient density within different constraints.

The chart below shows the micronutrient fingerprint chart for the highest-ranking plant-based recipes.

While these recipes will give people following a plant-based dietary approach a much better chance of living their best life, the maximum nutrient density approach is much better in terms of nutrient per calorie (as shown in the nutrient fingerprint chart below).  These recipes will enable you to eat fewer calories while still getting plenty of essential nutrients. This is ideal for someone who wants to lose weight while minimising cravings.  

The chart below shows the Optimal Intake Nutrient Score for all eighteen recipe books plotted versus percentage protein intake.  Not only does a higher percentage of protein align with greater satiety, but it also has the strongest correlation with nutrient density.  

So, if your goal is to lose body fat while getting enough of all of the essential nutrients (including the amino acids), then you want to move from where you are now to a higher percentage of protein in your diet.  To achieve this involves reducing foods that contain high amounts of carbs and/or fat while not avoiding higher protein foods.

There is a tipping point at around 50% protein (or a protein:energy ratio of greater than 3.0) where you start to get diminishing returns in terms of nutrient density. 

The High Protein:Energy recipes will maximise satiety but won’t provide optimal nutrient density, so they are probably only appropriate for someone wanting to lose body fat fast (e.g. someone who is morbidly obese or a bodybuilder trying to lose the last few grams before a show) before transitioning to a more sustainable nutrient-dense approach.  

The chart below shows that less fat aligns with a higher nutrient density.  Fat is a great fuel source but is not necessarily full of nutrients. If you are getting adequate protein and omega 6, you will be getting plenty of fat.  

When it comes to non-fibre carbohydrates, there seems to be an optimal intake somewhere between 15 – 20% of calories where nutrient density is maximised.  While there is no such thing as an essential carbohydrate and it is wise to titrate your carb intake to ensure stable blood sugars, many of the vitamins and minerals are easier to obtain from foods that also contain some carbohydrates.  

If you look at the photos below you will see that there is no lack of plant-based ingredients in the optimal recipes.  

Finally, we can see that nutrient density (in terms of essential nutrients per calorie) is also correlated with the energy from fat and/or carbohydrates in our diet.  If you have body fat that you want to lose you need to optimise your diet to move to the left on this chart. Incrementally lowering the fat in your diet will allow your body to use stored body fat.  

It’s about Optimisation and context 

Optimisation depends on your context and your goals.  It’s not simply about targeting one parameter (such as protein, mTOR, IGF-1, carbs, fat, etc).  

Some useful parameters you can use to optimise your diet are:

• waist-to-height ratio (ideal is about 0.5),
• blood sugars (ideal waking is less than 100 mg/dL or 5.6 mmol/L), and 
• body fat percentage (ideal for men is less than 15% and less than 25% for women).  

You don’t need to be as lean as a bodybuilder about to step on stage or look like someone who has been locked in a concentration camp.  Your goal should be to have enough lean mass without excess fat body fat.   

Your life trajectory

When it comes to healthy aging, you need to think of what you want to look and feel like at 70 or 80.  Do you want to be independent? Do you want to be able to hold your great-grandchildren? Strength will decline with age past 30 or so.

To achieve health and independence in the real world later in life, you should ideally think of your lean muscle mass as a bank account that you deposit in and draw down on as you age.  

A great example of this in practice is my friend Ian (Pa) Rambo, who, at 64, is still eating and training for optimal body composition and performance.  

He is the older competitor on Ninja Warrior and has even set up a gym in his backyard so he can practice daily in his retirement.

Nutritional Optimisation Masterclass

In our Nutritional Optimisation Masterclass, we guide Optimisers to progressively dial in their current diet over six weeks to ensure they are moving towards their goal.  

After tracking their baseline diet, we encourage them to ensure they are getting at least 1.4 g/kg LBM of protein.  This is a reasonable minimum intake to prevent loss of lean muscle and promote satiety.  

From there, we dial in carbohydrates to ensure that we are getting stable blood sugars (i.e. a variation of no more than 1.6 mmol/L or 30 mg/dL before and after meals).  It only takes two or three weeks for most people to start seeing excellent blood sugar results. The rate of fat loss tends to accelerate once we have drained the excess glucose stores from the bloodstream.  

From there, we dial in fat intake to ensure you are achieving your weight loss goal.  

During aggressive weight loss, it’s important to keep an eye on body fat and lean body mass.  

If you are losing an excessive amount of precious lean body mass the Smart Macros Algorithm will recommend that you dial up your protein to slow the rate of muscle loss.  

This is critically important in terms of appearance, metabolic health and managing appetite.  Your body will respond aggressively with an increased appetite if it senses that it is losing too much lean mass.  

Finally, we guide people to ensure they are meeting their minimum intake of all the essential micronutrients and then guide them to strive for the Optimal Nutrient Intakes that aligns with greater health and satiety.  

NAD+ supps are big business 

A couple of years ago, when I initially looked into NAD+ supplements, I was super bullish and even bought some stocks in Chromadex who owned the patent for Nicotinamide Riboside, and even considered trying to get a stockpile of it to be a distributor.  

But after a while, I saw study after study that failed to demonstrate any benefits of NAD+ supplementation in humans over and above plain old niacin (which is dirt cheap).  

As with most supplements, increasing the levels of substance XYZ in your blood to look like you are younger on paper rarely equates to the same outcomes as the health improvements that would actually lead to your body raising that substance naturally.  Just managing a marker with a supplement does little for our health.  

Most people can convert dietary niacin and tryptophan in their diet to NAD+ so long as they are getting enough.  Our satiety analysis shows that more than about 80 mg of niacin per day doesn’t align with greater satiety and likely does not align with greater health.  

Your appetite stops seeking out foods that contain more niacin.  Above this level, your kidneys just have to work harder to clear the excess, regardless of whether it came from food or a pretty bottle that you paid a lot of money for.  It all ends up in the toilet! 

While our stretch target of 70 mg per day for vitamin B3 is above the average population intake of 44 mg and the Dietary Recommended Intake of 16 mg, it is definitely achievable with a nutrient-dense diet (which will likely come with all the other beneficial nutrients and cofactors that your body needs to use niacin effectively.  

If you supplement with high doses of niacin, be prepared for a surprising and sometimes uncomfortable ‘flushing reaction’ as your body heats up for an hour or two like an internal sauna.  However, you will not experience this if you get optimal intakes from food. Your body likely uses it much more efficiently across the day.  

Foods to eat to raise your NAD+ levels 

Ironically, the dietary precursors to NAD+ (niacin and tryptophan) are higher in animal-based foods.  A diet with a high percentage of protein will lead to greater satiety and lower spontaneous energy intake, which will increase your NAD+:NADH ratio.  

A plant-based diet with avoidance of protein is likely to lead to a decrease in NAD+ and hence the perceived need to supplement in the hope that exogenous supplementation will provide the same benefits as the endogenous NAD+ produced by your body in a lower energy state with adequate nutrient density.  

As shown in the biochem pathway below, NAD+ is made in your body from niacin (i.e. vitamin B3) and tryptophan (an essential amino acid) with cofactors magnesium, B6 and B2.  If you wanted to invest your money in food rather than supplements, what types of foods would you want to eat to get more of these nutrients in your diet?

Listed below are the foods that contain more of these nutrients per calorie:

Plants

• spinach
• mushrooms
• asparagus
• parsley
• zucchini
• coriander/cilantro
• broccoli
• cauliflower 
• green peppers
• lettuce
• celery
• bell peppers
• pumpkin seeds
• Brussels sprouts
• radish
• sour pickles
• kale
• sauerkraut
• cabbage
• dill pickles
• cucumber

Animal & Seafood 

• beef liver
• lamb liver
• tuna 
• chicken liver
• salmon
• chicken breast (no skin)
• sirloin steak (fat not eaten)
• mackerel
• egg white
• shrimp
• chicken  
• sardines

Micronutrient fingerprint

The micronutrient fingerprint chart below of the NAD+ boosting shows that these foods show that these foods are actually very nutrient-dense and (ironically) have a very significant amount of protein (i.e. 55% of calories).  Consuming more of these foods will supply your body with more of the essential nutrients that you need to produce NAD+ in your own body. With more protein, a lower energy density and less easy energy from fat and carbs, these foods will also be incredibly satiating and enable you to eat fewer calories, thus raising your endogenous production of NAD+ and your NAD+:NADH ratio.

NAD+ Boosting Nutrition Program

If you’re interested in consuming more food and meals that will help you increase your nutrient density, satiety and NAD+ without relying on expensive supplements, we have prepared a simple pack with contains:

• An index of 150 nutrient-dense recipes that contain more of the nutrients that will enable your NAD+ naturally,
• A Nutritional Optimisation Program to guide you through the process,
• A list of the 50 most popular foods that provide more of the essential nutrients required to produce NAD+ in your body, 
• A list of 100 popular foods that provide more of the essential nutrients required to produce NAD+ naturally in your body and 
• A longer list of 150 foods that provide more of the essential nutrients required to produce NAD+ in your body to enable you to diversify your food choices further and level up your nutrition once you get used to consuming more of the most popular and popular foods.

Can you buy health and longevity in a pill? 

Selling hopes and dreams has been a profitable business strategy for a long time.  

Who knows if Sinclair and his colleagues will ever be able to demonstrate that their anti-aging supplements provide any tangible benefits in humans beyond just temporarily raising the levels of NAD+ in your bloodstream?  Regardless, you have no business blowing your hard-earned cash on supplements if you’re not already doing everything you can to optimise your diet and lifestyle first.  

It’s unlikely that using exogenous supplements to modify particular markers in the blood has the same effect as optimising your diet and lifestyle to ensure your body produces those things endogenously as part of a healthy system.  Supplementing with exogenous NAD+ to increase Sirtuin action is like paying your cleaners a whole lot of extra money to come in and dust your house while it is still stuffed to the rooftop with garbage.  

Another recent “health” craze that made a few people a LOT of money was exogenous ketones.  Taking exogenous ketones to raise the levels of BHB in your blood is akin to getting a bottle of someone else’s sweat and sprinkling it all over yourself and thinking you had a great workout.  In a similar way, the majority of the benefits associated with ketosis only occur when they are being produced inside your body due to an energy deficit because you’ve found a way of eating that allows you to eat less and maintain healthy body composition.  

Most of the compounds that have been found to be beneficial are extracted and concentrated from plants.  One of Sinclair’s early discoveries was resveratrol, which was popular until they realised that in humans, the amounts you could get in a capsule were ineffective, and you would have to drink crates of wine daily to get any meaningful effect.  

In Lifespan, Sinclair notes that many of the compounds we have found to be beneficial (e.g. resveratrol, sulforaphane, phytochemicals, etc) occur in stressed plants and cause small beneficial (hormetic) stresses in our bodies.  These “stressed” plants also tend to contain plenty of nutrients that they have had to grow long roots to extract from deep in the soil to survive in harsh conditions.  

Unfortunately, these days, it’s only the boutique winemakers (viticulturists) that seem to understand the connection between nutrients and flavour, with the rest of our food being grown to maximise energy production, with artificial chemicals and flavours added to cover for the lack of taste and nutrients.  

Supplements never seem to come in the form that your body is accustomed to and, hence, aren’t absorbed in the normal way.  You either get too much of them, and your kidneys have to work harder to flush them (into the toilet). Alternatively, they come in such small quantities that they don’t have a significant effect.  You really need to find a way to ensure these nutrients are contained in the foods you eat every day to get meaningful amounts of them. 

In the end, you are wasting your money when you could be spending it on real food that contains meaningful quantities of those beneficial nutrients.

Conclusion 

So, to summarise this rant:

• We cannot transpose research on yeast and mice (living in captivity with externally controlled diets) onto free-living humans who can eat whatever they want whenever they want.  If you are able to eat until you are no longer hungry, it is critical to optimise your diet for maximum satiety to reduce your reliance on your limited willpower.  
• Maintaining a healthy level of body fat and muscle mass is smart.  Voluntary starvation to the point of malnutrition and sarcopenia is not.  
• Increasing the number of essential nutrients per calorie (i.e. nutrient density) is an excellent strategy to increase satiety.
• Targeting more protein will not necessarily lead to increased satiety.  However, a higher percentage of protein will lead to greater satiety and align strongly with nutrient density.  
• Good nutrition and maximising your health span are context-specific.  You will be set up for a long and healthy life if you look after a waist-height ratio with healthy blood sugars, healthy body fat, and lean muscle mass.  
• Longevity supps, diet fads and snake oil crazes come and go.  However, studies showing the benefits of these relative to a healthy diet and regular activity are hard to come by.  
• If you are not already doing everything you can to optimise your nutrition and body composition, you are wasting your money, energy and hopes on supplements.  You may just find that once you optimise your nutrition, you have no desire or need for a “magic pill”.

More

• Protein for weight loss: How much you need and why it works
• Want to live forever? Factors influencing longevity.
• Highest Niacin (Vitamin B3) Foods and Recipes
• Optimal foods for fat loss
• What is Nutrient Density (and Why It Matters)?
• Micros Masterclass