humanOS Year in Review (Part 2 of 3): Hot Topics in Nutrition in 2018

In the last blog we began by reviewing how humanOS evolved in 2018. We ended by focusing on what we learned in 2018 about the science of aging. In this post we turn our attention primarily to new developments in the science of nutrition, picking up where we left off as we consider how diet affects aging.

How diet affects how we age has received a lot of airtime this year. Because humans live for so long and aren’t very good at sticking to lifestyle interventions, most research on diet and longevity has been done on other animals. Dan discussed one of these studies with Susan Westfall, who found that fruit flies that consumed an Ayurvedic supplement plus certain probiotics lived dramatically longer than other flies.

Such preclinical studies are very interesting and can pave the way for research on humans, but we should always be wary of assuming that it’s possible to use other organisms to model how humans respond to various stimuli. I wrote about this a little in a two-part blog (1 2) in which I shared some of my reservations about making this leap as I discussed the importance of dietary protein as we age. My thoughts on this topic seem to generally converge with those of Stuart Phillips, with whom I had a great time speaking. One talking point that came up was whether eating insects supports skeletal muscle mass and health. Earlier, I wrote about this on the blog, highlighting some noteworthy considerations, foremost among which is the fact that eating insects is much more sustainable than relying on foods such as meat.

Like my conversation with Stuart Phillips, Dan’s conversation with Keith Barr also focused on skeletal muscle mass. Much of their back and forth was about how to ensure that we exercise and eat to support the health of connective tissues such as tendons.

I’ve had first-hand experience of musculoskeletal problems, and as a teenager I experienced back pain intermittently. I was therefore very happy to speak with Stuart McGill about his work on spine health and performance. His research and books have strongly influenced my thoughts on physical activity and exercise training over the years. Stuart drills home the importance of first moving well (don’t “pick the scab”!) and not adding fitness to dysfunction. To give an analogy that might help instil the latter idea, think of the muscles of your torso as a car’s engine and your spine as the vehicle’s chassis. Well, you wouldn’t want a car with a powerful engine and a flimsy chassis, for you’d probably soon write the chassis off. I frequently hear people say things like “back strength is key to avoiding back pain. So, go do some deadlifts!” I enjoy deadlifting as much as the next person, but this advice is often misguided.

Antioxidants are another topic about which there has been much confusion over the years. Dan’s discussion of antioxidants with Michael Ristow is one of my favorite humanOS Radio episodes of the year. I remember enjoying reading Michael’s 2009 PNAS paper during my undergraduate degree, so it was great to hear his thoughts on a range of interesting matters. In the blog that accompanies the podcast, we included additional information about many of the compounds discussed, should you be interested in more information on them.

This year, we tried to share some simple nutritional strategies to enhance athletic performance on the blog. One of these is taking creatine monohydrate. This blog was necessarily long, for there is simply so much evidence that creatine supplementation improves numerous facets of health and performance. Earlier, I wrote about what I thought was a fascinating study showing that rats fed creatine slept less and had shallower sleep too. What’s truly remarkable is that whereas sleep loss consistently degrades perhaps all aspects of human biology, in many ways creatine supplementation seems to have the opposite effects, despite its effects on sleep.

Creatine supplementation seems to be good for the health and function of the brain, and many people’s interests in compounds with these properties grew this year. I’d noticed that when I consume substantial quantities of cocoa or dark chocolate my mood and productivity surge, and it turns out that there’s a substantial body of evidence showing that cocoa has these effects, as I reviewed here. As I read about other plants with similar effects, Bacopa Monnieri piqued my curiosity given its safety profile and positive effects on cognitive function.

Another nutritional strategy that we reviewed is dietary nitrate supplementation. Dan interviewed Jonathan Burdette about a fascinating study Jonathan’s research team did showing that adding nitrate-rich beetroot juice supplementation to a walking-exercise program made the patterns of blood flow in the brains of elderly people more closely resemble the brains of younger people. I then went on to overview the effects of dietary nitrate on exercise performance and general health, including that of the brain. In short, don’t skimp on consuming nitrate-rich vegetables such as beetroot and spinach!

Has there been a hotter nutrition topic in the online health and fitness community this year than ketosis?

If there has, I’ve somehow missed it.

Interest in ketosis has spiked for many reasons, one of which is its potential efficacy in treating metabolic diseases. In this podcast, I think Dan and Stephan Guyenet did a tremendous job of dissecting a recent study that showed that ketogenic diets can help treat type-two diabetes. In a later episode of humanOS Radio I spoke with Tommy Wood about another therapeutic use of ketones – treating brain injury. But people aren’t only interested in using ketones for medical purposes, and there’s also been some hype about whether ingesting ketone supplements enhances athletic performance. I wrote about this here. Regardless of your reasons, if you’re keen to try a ketogenic diet, Dan made a guide on ketogenic diets that Pro members can access here.

Now, interest in some dietary approaches waxes and wanes dramatically. But people are always interested in alcohol. Back in August The Lancet published a paper provocatively entitled “No level of alcohol consumption improves health”. This predictably caused a stir, and in this blog Ginny coherently strung together her thoughts on this contentious subject. At the same link you’ll also find Dan’s interview with Todd White from Dry Farm Wines. If you’re going to drink, wines made without added sugar are often an excellent choice.

There’s marked variability between people in how well they detoxify alcohol, so while some people appear to suffer no ill effects from a few drinks here and there, others quickly become disorderly. Just visit England if you want to see this for yourself. Anyway, this exemplifies the importance of personalizing nutrition, and new companies providing tests designed to provide bespoke dietary guidance are emerging left, right, and centre. Personalized nutrition is a complex research field, and Dan briefly explored one corner of it in this conversation with Alon Keinan about genetic variation in how efficiently people’s bodies construct certain fatty acids.

One of the reasons many of us became interested in diet was to feel better about how we look. In truth, much of what we’ve shared this year can help you if your goal is to improve your body composition. But three blogs that Ginny wrote are particularly relevant to those of you wanting to shed fat.

The first of these reviewed a study that showed that despite their high calorie density, walnuts are very satiating and may therefore be a smart choice for those of you who wish to stay lean. Ginny’s next post critiqued a study that reported that drinking sparkling water considerably increases blood concentrations of ghrelin, a hormone that typically increases food-seeking behavior. The careful student that she is, Ginny didn’t take the authors’ conclusions at face value though, pointing out some noteworthy limitations of the study. And in the last blog I’ll mention here, Ginny summarized findings that while after people do cognitively demanding work they’re liable to eat more at a buffet, doing strenuous exercise in the period between the cognitive task and the buffet offsets this effect in the short-term. One more reason to build physical activity into your day!

Finally, one behavior common among people who sustain substantial weight loss is that they weigh themselves regularly. But is the way that most of us weigh ourselves optimal? Well, Dan spoke with Dan Ariely about Shapa, a novel weighing scale that may help people rid themselves of unwanted pounds by overcoming some limitations of traditional scales. You may want to tune in if you’ve been overindulging over the festive period!

Fundamentally, changes in how fat you are depend on fat balance, the difference between how much fat your body stores and how much it burns. So, a simple way to tip this balance in favour of fat loss is to simply not eat! But while fasting can certainly be a useful strategy for people who wish to rid themselves of inches off their waists, intelligent use of fasting may have numerous other favourable effects on health too. The question is, what are some smart ways to implement fasting?

In our guide to fasting, Jeff Rothschild (lead developer of our fasting program) and Dan summarized a variety of different fasting protocols, including a method used to mimic the effects of fasting without enforcing a true fast. And if you aren’t a Pro member, you can still read more about one of these approaches in this blog that Ginny wrote.

That’s all for now. In the final part of this series we’ll review what we’ve learned about circadian rhythms, sleep, and the brain, ending by looking ahead to what’s on the horizon for humanOS in 2019.

Watch this space!

Make 2019 your best year yet in your pursuit to master your health. Pro membership of humanOS.me costs just $9.99 per month, and Pro membership gives you access to all our courses, how-to guides, tools, recipes, and workouts. Pro members also support our work on blogs and podcasts.

In my last blog I focused on dietary protein and aging, introducing several concepts that are foundational to the main subject of this post: dietary protein and cancer. So, if you haven’t read the previous blog then I strongly suggest you do so before reading this one. After exploring some of the research on dietary protein and cancer, I’ll end by tying together what I’ve discussed as I share my current perspective on all of this. Without further ado, let’s get to it.

In a highly-publicized study of more than 6,000 US adults aged 50 years plus, a group of researchers reported that among people aged 50 to 65 years, participants reporting the highest protein intakes had a 75 percent increase in mortality and a 4-fold increase in risk of death due to cancer over a period of 18 years. Whoa. Somewhat strangely, higher protein intakes were associated with reduced cancer and overall mortality in people aged over 65 though. Analyses suggested that consumption of proteins from animal but not plant sources contributed to associations with risk of mortality and cancer. The scientists concluded that low protein intakes are best in middle-age, but high protein intakes might be preferable in elderly people.

When the University published a press release for this study, the supposed adverse effects of higher protein diets were likened to smoking. I don’t know about you, but to me that sounds hyperbolic.

As more people read the paper, many of the world’s foremost experts in dietary protein expressed reservations about the study. Curiously, the journal in which the study was published refused to publish some of these, including a letter by Stuart Phillips and several of his colleagues. Among others, they made the following points:

The dataset from which the data came contains information for almost 12,000 adults. The researchers eliminated almost half of the data but didn’t elaborate on why.

The researchers reported that “…the level of protein is … not associated with differences in all-cause, cancer, or cardiovascular disease mortality.” But cancer mortality was actually numerically about 10 percent higher in the low protein group than in the high protein group. This is very interesting when you consider that the scientists then did a series of experiments on mice and yeast to look at why they think dietary protein increases risk of cancer. That’s a head-scratcher.

Finally, this point is worth dwelling on: To arrive at their conclusions, the authors used a single 24-hour dietary recall to assess diet over the entire 18-year period. Think about what you ate yesterday. Is that likely to be representative of your typical diet in the coming 18 years? If the answer is yes, more power to you. You are a machine.

More than anything, I’m highlighting these limitations to emphasize how important it is to be discerning when interpreting information about health – even information in prestigious academic journals. And while I don’t want to cry foul of any misdemeanors, it is relevant that the senior author on the study has created a line of low-protein, plant-based, “fasting mimicking” products. My understanding is that he doesn’t profit from sales of these products. But the profits do fund his research. And he does profit from sales of his book on how to eat to live longer.

Again, I’m categorically not saying there has been any bad play. But there’s no harm in being skeptical and considering ties and incentives.

With all of that said, might high-protein diets predispose people to cancer? The first point to make is that cancers are stupendously heterogeneous. In the interest of brevity I need to paint with broad brush strokes in this blog, but please be aware of this.

Some amino acids are directly implicated in accelerating tumor growth in other animals. Leucine, for example, hastens pancreatic tumor growth in both lean and overweight mice. And restricting methionine intake tends to curtail prostate tumor growth in mice.

Overall, I think there is quite strong evidence that mTOR and IGF-I signaling is involved in tumor progression, and restricting protein intake might be a good idea for cancer patients, even if this speeds muscle loss. I’ll add that the in the journal article that I discussed above, the researchers followed up the cross-sectional study of humans with experiments on male mice injected with melanoma (a type of skin cancer) cells and female mice injected with breast cancer cells. They found that mice consuming higher protein diets had a higher incidence of tumors after the injections, as well as accelerated growth of these malignant growths. IGF-1 signaling was greater in the higher protein groups.

However, keep this in mind if you don’t have cancer: I’m aware of no data that show a causal role of protein per se in the development of cancer. And people with more muscle tend to be more likely to survive solid tumor cancers. One last comment though: Independent of amino acid composition, the sources of your protein intake are likely to affect your risk of some cancers (colorectal cancer, for example). But that’s a topic for another time.

These studies on aging pathways are very intriguing. And important. And fun to think about. (Maybe that’s just me).

As I reflect on them though, you can probably sense that I’m not drawn to the idea of a low-protein diet. I don’t really want to amble into the sunset skeletal and lethargic after years on a low calorie diet. I want years in my life and life in my years.

And think about our ecological niches as humans.

We aren’t yeast or roundworms in media.

Nor are we mice in cages.

We are bipedal, long-lived primates.

We live in rapidly changing environments that we aren’t necessarily well adapted to, the results of which include strong dispositions to chronic diseases. One of these is obesity, which particularly seems to instigate cascades of unfavorable consequences.

What else?

When we fall in old age, we fall hard. Especially if we are weak and pudgy.

So, I’m interested in staying strong and lean as the clock ticks on. My perspective is undeniably musculoskeletal system-centric, surely reflecting my background (I studied exercise science and sports nutrition before my PhD) and preferences (my independence is really important to me, and I care about how I look. How vain, I know).

Another factor has been the recent loss of my granny. I miss her. She lived a long, rich life, but understandably became very frail near her end.

What you value will surely differ, and you should of course use your goals to inform your choices. Perhaps, for example, you limit your intake of animal foods for ethical reasons. If so, you’re a better person than I am. And who knows, you might be doing yourself some good in the process.

You might also want to consider variables such as your family medical history. Let’s say that several of your family members have had sarcopenia and osteopenia. In this case, it might be important to optimize your resistance training and protein intake. But if several relatives have had been physically strong but then succumbed to cancer then this might nudge you to focus on different behaviors.

With all of this said, what factors have shaped my viewpoint? Consider these:

First, although lean body mass is likely to be reduced by long-term calorie restriction, the ratio of lean body mass to fat mass will probably be enhanced by caloric restriction, and this is surely a good thing for metabolic health. To be clear, I definitely think that intermittent calorie restriction is smart. Most people invariably gain a little weight during holidays, so if nothing else then calorie restriction is necessary to shirk any fat gained during these periods.

Please note that calorie restriction needn’t entail counting calories – simply consuming something like the Simple Food Diet or FLASH diet that Dan and Stephan detail in the Ideal Weight Program (available here) generally results in people inadvertently consuming fewer calories than they burn. And I’d rather have periods of high energy intakes too to provide plenty of energy to support exercise that is strenuous enough to produce many of the health benefits that counter the changes typically evident during aging. (Being perpetually depleted by a calorie deficit isn’t conducive to lifting heavy objects, doing hard interval training, or warding off coughs and colds while doing so.)

Second, consuming protein tends to quickly and substantially raise satiety hormones and hence how full people feel. As a result, tightly-controlled experiments have consistently shown that people tend to lose more weight when they consume higher protein diets.

Higher protein intakes therefore make it much easier to sustain calorie restriction. Both calorie intake and protein intake affect signaling through all of the pathways I’ve discussed, and it’s plausible to me that during calorie restriction, higher protein intakes combined with resistance training might increase signaling where you want it (in skeletal muscle) but have different effects in other tissues. After all, a well-known consequence of resistance training is increased amino acid uptake by the trained muscles. So, might the amino acid and appropriate training stimuli increase IGF-1 and mTORC1 signaling in muscle, while caloric restriction ensures that activation of these pathways is constrained in other tissues?

Keith Baar and Megan Roberts (who is part of the Nourish Balance Thrive crew – we love those guys) coauthored an interesting paper recently, showing that a ketogenic diet affects mTOR signaling in tissue-specific ways in mice. What we really need are studies looking at the amplitudes and kinetics of activation patterns of pathways like mTOR in different tissues in different animals subjected to different stimuli. Should be easy, I know.

Third, higher protein diets not only lead to greater reductions in fat mass in elderly people, those consuming more protein also lose less lean body mass. It’s not only the signalling pathways I’ve discussed that affect lifespan and healthspan – carrying less body mass and fat mass should beneficially many other processes involved in longevity, such as regulation of blood pressure, blood sugar, and blood lipids.

Fourth, older adults are more resistant to the muscle building effects of dietary protein. This dulled responsiveness of elderly muscles to stimuli that boost muscle protein balance has been dubbed “anabolic resistance”. For this reason, the advice to consume a lower intake of lower quality (in terms of digestibility and amino acid composition), plant-based protein in later life makes little sense to me.

Fifth, during fasting, mTORC1 activity drops, and this fluctuating mTORC1 pathway activity is probably integral to good health. Good news: well-timed meal patterns seem to be good for all sorts of things, as I discussed in previous blogs on chrononutrition (1, 2, 3) as well as in the circadian course program. Jeff and Dan also spoke at length about this subject in the fasting course. (Note that our courses are available for Pro users.) Anyway, one way of accomplishing this is using time-restricted eating, which seems to improve mTOR pathway function in mice fed poor quality diets. I’ll add that a very rigorous study was published last year showing that when mice are fed calorie restricted diets, they voluntarily shorten their feeding periods too – they self-impose time restriction. This work was remarkably comprehensive and raises questions about whether it is actually time restriction that accounts for many of the benefits reported in studies of calorie restriction in other animals.

There are of course so many other things to consider that I haven’t mentioned too, and my perspective hasn’t been shaped by any systematic literature review or attempt at assessing all of the factors currently known to influence longevity, healthspan, and quality of life. (As an aside, you should check out this resource if you want to explore the most troublesome health challenges that people face worldwide.)

So, take my thoughts with a pinch of salt.

Nevertheless, synthesizing the above, if I was elderly and relatively healthy then I would prioritize resistance training and periodically restrict my calorie intake. I’d probably almost always restrict the period in which I consume calories each day too. But I’d still consume a relatively high protein diet. To be honest, I already do these things, but I’d tweak the specifics of my behaviors. I’ll add that there are many nuances regarding optimizing protein intake for different ends. I’ll be addressing these in the upcoming course on dietary protein.

Well done for making it this far. This has all been percolating in my mind for a few years, so it’s been a pleasure to jot down some ideas. I’m very open to other views, so please share opposing ones. These blogs are less prescriptive than some of my other work, but I hope you see why this is the case. This is a really consequential subject, and I plan to keep up with the research on it in years to come.

Stay strong… and think for yourself!

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In

, we briefly looked at how our circadian systems time our daily patterns of behavior and biology, as well as how the this clockwork is synchronized with the 24 hour day. In doing so, we discussed how the foods we eat, and the types and amounts of nutrients available, are key to synchronizing the clocks in many of our bodies’ tissues.

Today, we’ll delve deeper into this subject, exploring the many ways that when we eat influences our metabolic health.

We’ll focus in particular on studies of breakfast-skipping.

As we saw in Part 1, fasting/eating patterns produce changing levels of factors that circulate through the body, which can then modify the activity of the molecular clockwork that times the metabolic reactions in our cells. In this way, abrupt fasting/eating cycles facilitate robust rhythms in both our biology and our behavior. These strong rhythms are characteristic of a healthy circadian system, and we see this clearly in rodents.

When mice are fed high-fat high-sugar diets to their hearts’ content, these animals consume a greater proportion of their food during times when they would normally be inactive and fasting. This prolonged feeding period (more time each day in which food is being consumed) instigates rapid changes in daily gene expression and produces multiple adverse metabolic consequences, including fat gain, insulin resistance, and impaired lipid regulation, increasing fat deposition in the liver (1).

Promisingly, however, in all of these instances, “time-restricted feeding” (typically restricting food access to a period of 12 hours or less each day) confers all sorts of benefits to metabolism in mice. (In the soon-to-be-released course on fasting on humanOS, Dan and Jeff Rothschild refer to this as a shortened eating window. In these blogs I’ll refer to time-restricted feeding when discussing other animals and “time-restricted eating” in reference to studies of humans.) Restricting the feeding period in mice often leads to lower body fat and lower cholesterol levels, as well as higher insulin sensitivity (2).

But what about humans?

In contrast to rodents, it is less clear whether time-restricted eating benefits metabolic health in humans. Among healthy adults, confining daily food intake to a single evening meal has been shown to impair blood sugar regulation and increase blood pressure, cholesterol, and hunger in comparison to consumption of the same diet split into three meals each day (3, 4). This implies that drastically shortening the eating period to just one meal each day may not be the best thing, but might less severe time restriction still be useful?

Such controlled conditions may not be feasible for most of us, and people using time-restricted eating may eat less when left to their own devices: Some studies have shown that skipping breakfast (a form of time-restricted eating) reduces the number of calories people consume each day. However, this is offset by declines in physical activity, and careful studies have found that the primary effect of breakfast-skipping (in people that are not living in a lab setting) may be impaired blood sugar regulation, if anything (5 6). Perhaps the largest well-controlled trial exploring the effects of breakfast-skipping on weight loss in obese adults found that people did not lose additional weight when skipping breakfast (8).

Perhaps you noticed that in the aforementioned studies people began eating later in the day. Well, could the timing of the eating period affect health? If, for example, the eating period is 10 hours, would it matter if it starts at 06:00 or 12:00?

In mice, when researchers restrict access to fructose to the period when mice are typically asleep, the rodents develop insulin resistance and gain fat in comparison to mice that have access to the fructose only during the period when they are active and normally eat (8). Similarly, restricting access to a high-fat, high-sugar diet to the time when mice usually sleep tends to lead to greater body fat. Doing so also flattens daily hormone rhythms and reduces energy expenditure and fat oxidation (9).

Not good.

Diet timing within the active period may also matter, as mice fed a high-fat, high-sugar “meal” at the end of their day (active phase) gain more fat and are more insulin resistant than mice fed this same type of meal earlier in their day (10). This may be related to misalignment between energy intake and expenditure. Researchers can change the genetics of mice such that their clocks run more quickly, meaning that the mice they have internal days significantly shorter than 24 hours. When such mice feed at will, they consume many of their calories well before their physical activity peaks and promptly become obese. But if the mice are only given food near the time of peak physical activity, they do not become obese (11). The implication for us is that eating in close proximity to physical activity may have beneficial metabolic effects.

But is this another case of mice and men differing in responses?

Maybe… but maybe not.

In a controlled trial, overweight and obese women who consumed a larger proportion of their daily intake earlier in the day had greater improvements in blood sugar and lipids and lost more weight than those consuming more later in the day (12). Furthermore, eating lunch earlier has been associated with greater weight loss in cross-sectional studies (13). The finding that diet-induced thermogenesis (the increase in metabolic rate that follows eating and drinking) is higher earlier in the day (14) may help explain these findings. Other studies designed to unmask the roles of the circadian system in metabolic regulation have shown that many metabolic processes (such as glucose metabolism) are optimized relatively early in the day. And findings from the previously discussed Bath Breakfast Project studies also imply that eating earlier in the day may stimulate more daily physical activity, although this needs further testing.

Collectively, these findings support a possible benefit to assigning more of your daily energy intake to the first half of your waking day, although there may be caveats. First, although confounded by myriad factors, not the least of which is an emphasis on abstinence from overeating, Ramadan studies often show that people lose weight when they can only eat during darkness (15). Second, time-restricted eating studies have often lacked objective measures of body composition. Third, as melatonin is synthesized during darkness and may acutely impair insulin signalling (16), it may be wise to avoid eating so late or so early that it is your body’s biological night (17) ( see this blog for more on this). This is particularly relevant for alarm-clock users and night shift workers.

We tend to make poorer decisions when our circadian systems are misaligned and our sleep has been disrupted. Many people are improving our understanding of how this influences our dietary decisions, including Dan.

Finally, intermittent fasting (not necessarily synonymous with time-restricted eating) is a promising metabolic therapy for many disease states and may be an effective prophylactic when used wisely (18).

In the next post in this series, we will consider the impact of eating at consistent times on a day-to-day basis, as well as how certain dietary components can alter circadian rhythms (for better and for worse).

More to come!