When it comes to muscle health, the verdict is in. As discussed in my book, “Hold On to Your Muscle, Be Free of Disease,” animal protein has a greater anabolic effect than plant-based proteins. But what about overall health and longevity? Does a diet high in animal protein increase the risk of cancer and shorten lifespan? Alternatively, does eating more plant-based proteins protect against cancer and other age-related diseases?
Before we dive into the latter more controversial issues, let’s first look at the evidence supporting the superiority of animal protein in muscle health and maintenance. A recent critical review covers this topic well. The quality of dietary protein is determined by its amino acid composition, digestibility, and availability for skeletal muscle protein synthesis. Two methods are used to assess protein quality: PDCAAS (Protein Digestibility Corrected Amino Acid Score) and DIAAS (Digestible Indispensable Amino Acid Score). A PDCAAS score of less than 100% indicates that a protein cannot meet human amino acid requirements. While animal proteins score 100% (or very close), plant proteins (excepting soy protein isolate) come in under 100%. The PDCAAS score for wheat gluten, for example, is only 25%. The DIAAS score is also lower for plant proteins (i.e., under 100%).
One reason for the lower quality scores of plant proteins is that they are less digestible than animal proteins. Plant proteins are attached to fibers which obstruct the activity of digestive enzymes. Antinutritional factors such as phytic acid in plants affect digestibility as well. Apart from the digestion factor, plant proteins have incomplete amino acid profiles. While they do contain all of the nine essential amino acids, some of them are limiting, i.e., below human requirement. For example, grains are limiting in the essential amino acid lysine while legumes are limiting in the sulfur amino acid methionine. These limiting amino acids can limit muscle protein synthesis because all the other essential amino acids cannot be fully utilized for protein synthesis and are thus ‘wasted.’ Furthermore, plant proteins have less leucine than animal proteins. Leucine is a key trigger of muscle protein synthesis.
Both animal and clinical studies in the review have found that single plant proteins are less effective than animal proteins at triggering protein synthesis in skeletal muscle and at inducing muscle hypertrophy (gains in mass). However, most people who eat a plant-based diet consume different sources of plant proteins rather than a single protein source. Deficiencies in one type of protein (e.g., legume) can be offset by other proteins (e.g., grains) and vice versa. Importantly, however, the quantity of plant-sourced protein must be significantly increased to 30 grams/meal or more to improve their capacity to support muscle mass maintenance, particularly in older adults.
According to Dr. Donald Layman, noted authority on dietary protein and amino acids, a person on a plant-based diet needs to consume about 120 grams of protein per day to meet amino acid needs for muscle health. On an average omnivorous diet, men consume about 90 grams of protein per day while women eat about 80 grams per day. Unfortunately, most plant-based dieters decrease both the quantity and quality of dietary protein. Due to factors such as blunted appetite and chewing difficulties, consuming greater quantities of plant proteins to support muscle heath may be difficult for older adults.
There are other reasons to prioritize animal protein over plant protein. Anabolic resistance makes it more challenging to meet amino acid needs for muscle health in older adults. The response of aging muscle to anabolic stimuli is less robust in older adults compared to younger adults. Relying on only plants for protein is difficult enough without dealing with anabolic resistance. It seems logical for older adults to include sufficient high-quality animal protein in their diets to prevent sarcopenia – the age-related loss of muscle mass and strength. Cattle and other ruminant animals are critical components of our food system. Layman notes that they are capable of upcycling 60 grams of lower quality plant protein to 100 grams of high-quality animal protein providing the full gamut of amino acids to meet human requirements. Notably, the plants that the ruminants feed on are not suitable for human consumption (for those who think we should get rid of ruminates and just eat the plants). In a nutshell, humans evolved to eat more concentrated high-quality animal protein. By avoiding meat in particular, you’re missing out on some valuable functional nutrients (e.g., carnosine, taurine, and creatine) with antioxidant and anti-inflammatory benefits. … not to mention collagen for skin, joint, and bone health.
While a website dedicated to the promotion of plant proteins also refers to the benefit of mixing different plant proteins, it does not make mention of the need to eat larger quantities of plant protein, especially in older individuals, to increase its anabolic potential. Moreover, it cites four studies that support the ability of plant proteins to match whey protein for building and/or maintaining muscle mass when consumed along with resistance training or intense mixed martial arts training. However, the sources of plant protein used in the studies were powdered concentrates or isolates of either rice or pea protein. Unlike the actual plant foods (rice and peas), these purified powders are devoid of fiber and other plant components that would otherwise impair their bioavailability. Thus, while these supplements of plant protein were shown to be as effective as whey protein, most people eating a plant-based diet are eating the whole food and not purified supplements.
Another notable observation about these studies is the young ages of the participants. Most were college-aged men while some were in their 30’s. In young adulthood, asserts Layman, growth hormones such as insulin and IGF-1 are the dominant stimuli of mTOR – the master regulator of muscle protein synthesis. Accordingly, young adults can build muscle regardless of protein quality. On the other hand, older adults must rely on protein quality to buffer the loss of growth hormones that begins around the age of 30. The ability of plant protein supplements and blends to prevent muscle loss during aging is unknown and needs to be investigated.
All in all, while animal protein is more anabolic than single plant proteins, blending complementary plant proteins may be able compensate for amino acid deficiencies, provided one eats a larger quantity of protein to the tune of at least 120 grams per day (male or female). Of course, this translates to more calories and more carbohydrates.
So what about the association of high animal protein with cancer and mortality?
Let’s start with the largest review ever published (in the Annals of Internal Medicine) on the health impacts of red meat. This rigorous and exhaustive review concluded that the evidence linking meat to disease and premature death is too weak to recommend adults eat less of it. The review included both interventional and observational studies and included millions of participants over 34 years. The summary recommendations were that adults should continue rather than reduce their current consumption of unprocessed red meat and processed meat. To me, this major review of studies just reinforces the profound limitations of observational studies which comprise most of the anti-meat evidence in the review. Observational studies cannot determine causation; they are flawed in design due to unreliable food frequency questionnaires; and they are confounded by the healthy user bias.
The review consists of 6 papers: the summary article above; 3 reviews of observational studies, here, here, and here; a review of randomized trials; and the last paper on preferences regarding meat consumption.
Of course, there was a huge backlash from the plant-based world, as reported in JAMA. Criticism came from the Harvard School of Public health and from the True Health Initiative (THI) group headed by David Katz, MD who wanted the study retracted before publication. Interestingly, many individuals associated with the THI4, including Katz, have ties with plant-based companies. This is the letter from Katz and Harvard researchers sent to Christine Laine, editor-in-chief of the Annals.
One study by Levine et al. often mentioned when discussing high animal protein vs. low protein diets found that low dietary protein was associated with a significant reduction in cancer and overall mortality in people aged 65 and under but not in those over 65. In my book, I noted a letter written by leading protein researchers (including Dr. Donald Layman whom I interviewed for the book) that raised serious concerns about the study. See Protein Experts Respond to Recent Anti-Protein Claims | Biolayne. For example, they noted the following: “In their study, Levine et al. indicate that “…the level of protein is … not associated with differences in all-cause, cancer, or CVD mortality.” In fact, the data demonstrate that cancer mortality was actually ~10% higher in the low protein group compared with the higher protein group (i.e. 9.8% versus 9.0% deaths). We would argue that these obvious findings are the most important.”
Another problem noted by the protein experts is that the low protein group is < 10% of total calories. According to the Institute of Medicine, the AMDR (Acceptable Macronutrient Distribution Range) for protein ranges from 10% to 30% of daily energy intake. For the sake of comparison, the average protein intake during Paleo times was 37% of calories. I believe the current evidence strongly suggests that 10% protein is not enough to prevent sarcopenia in older adults. Furthermore, the scientists point out the use of only a single 24-h recall to derive dietary data to represent food intake over the 18-yr period of life seems highly unreliable. Their conclusion: the study is biased and flawed.
All that being said, if we assume the study findings are true (but we really don’t know this because association does not mean causality), a strong argument can still be made that we would be much better off eating high animal protein throughout life because the absolute reduction in mortality would undoubtedly be lower as a result of the benefit you would have later in life. In other words, mortality is relatively low before the age of 65 but increases very nonlinearly after 65. The benefit of high protein later in life would dwarf the detriment of high protein before age 65.
It’s very important to note that the study findings that link a low protein diet during middle age with reduced cancer and mortality involve, at least in part, lower levels of IGF-1 and insulin – both of which are growth hormones stimulated by protein. The rationale here is that to prevent the growth of cancer cells it would seem favorable to have less hormones and other factors in your body that promote tissue growth. The study authors also associate the benefit of high protein in people over the age of 65 to lower levels of IGF-1 that are seen with advancing age. In other words, higher IGF-1 from higher protein is important in older age groups to offset naturally declining IGF-1 levels and associated weight loss and risk of frailty.
The assertion that high animal protein causes adverse health effects via IGF-1 and insulin, as well as through increased mTOR activation (mTOR is the key regulator of muscle protein synthesis), is a major point of debate regarding the animal protein-disease controversy. In general, there are two camps: (1) Longevity researchers who advocate a low protein diet to inhibit mTOR signaling (mTOR inhibition is linked to longevity and disease prevention); (2) Leading protein researchers who advocate high animal protein (blowing way past the RDA) for optimal muscle health to maintain lifelong functionality and vigor and delay sarcopenia and frailty.
According to a review, mouse studies have shown that protein restriction is associated with longevity and metabolic health. Restricting specific amino acids can also impact health and longevity. For example, low circulating levels of branched-chain amino acids (BCAAs) were correlated with lifespan extension and better metabolic health in mice. Dietary restriction of the amino acid methionine was found to extend the lifespan of organisms ranging from yeasts to rodents. Food sources of animal proteins (e.g., meats, eggs, fish) have higher amounts of methionine and BCAAs than plant foods. Epidemiological (observational) studies such as the study by Levine et al. cited above have also linked high animal protein to increased mortality and diseases such as cancer and cardiovascular disease. Higher plant protein correlated with lower all-cause mortality.
Nevertheless, the authors of the review point out that “red meat is an important dietary source of micronutrients, including vitamins, iron and zinc; therefore, an appropriate intake is necessary to avoid malnutrition” and that “malnutrition, including sarcopenia/frailty due to inadequate protein intake, is harmful to longevity/metabolic health.”
Interestingly, as also noted in the review, the increased longevity among the people of Okinawa is often attributed to a low intake of animal protein. However, this is a classic example of the healthy user bias. It is likely that the longevity of the Okinawans is due to many other factors (e.g., a low-calorie intake, lots of vegetables, genes, and physical activity) and not the low consumption of animal protein (which is inferred only by association).
The common mechanism driving the longevity effects of the various forms of protein restriction is inhibition of mTOR – a major regulator of cell growth and proliferation. Protein, and particularly BCAAs, activate mTOR as well as IGF-1, which is part of the mTOR pathway. Overactivation of mTOR can contribute to tumor growth. We’ll go deeper into a discussion of mTOR in the next section.
High Animal Protein
In line with the main theme of my book, maintaining skeletal muscle mass is critical for preventing sarcopenia and optimal metabolic health. Activation of mTOR is the primary mechanism for inducing protein synthesis in muscle. With regard to dietary activation of mTOR, the rise in essential amino acids (especially BCAAs) in the blood after a meal is essential for switching on mTOR and subsequent muscle protein synthesis. Compared to plant- and insect-based proteins, animal protein (whey) was demonstrated to elicit a 2-fold greater rise in blood levels of BCAAs.
But won’t the activation of mTOR lead to cancer and accelerated aging?
First, it’s important to note that mTOR is also turned on by high levels of blood glucose and insulin and insulin resistance (1 in 3 American adults are insulin resistant). BUT there’s a major distinction between mTOR activation via protein (i.e., leucine) vs. via insulin resistance. mTOR activation from protein is a short-term acute response to a stressor. Similar to how a vaccine triggers an immune response, protein causes a temporary rise in mTOR that then wanes over a relatively short time. In contrast, insulin and an insulin resistant state cause dysregulated signaling of mTOR that persists indefinitely. Insulin activation of mTOR is like a “chronic hum” rather than an acute response as with protein.
Chronically activated mTOR is what leads to poor metabolic health and accelerated aging. This is attributed to consumption of excess calories, particularly from simple sugars. Conversely, chronic inhibition of mTOR from protein restriction can result in sarcopenia and frailty.
Additionally, consider that resistance training (RT) causes considerably more robust stimulation of mTOR than protein does. According to the protein restriction theory, people who weight train should have high rates of cancer. Quite the opposite is true.
Lastly, and perhaps most importantly, mTOR is tissue specific. While leucine (aka protein) is a unique trigger of mTOR in muscle, insulin activates mTOR in the liver and other tissues where it may be more likely to induce adverse metabolic effects from sustained activation. We want to intermittently trigger mTOR in muscle via protein and RT … rather than keep the mTOR “button” chronically pressed in the liver (through constant eating and excess carbs).
The are multiple paths to disease prevention and longevity. Based on animal and observational studies, protein restriction may be one path to consider. Some prominent longevity scientists favor inhibiting mTOR and other growth hormones (e.g., IGF-1) as much as possible to hopefully extend lifespan. Thus, they advocate restricting animal protein since it is a more potent trigger of mTOR than plant proteins. Also, high intakes of animal protein have been associated with cancer and other age-related diseases. [Note: I discuss the limitations of observational studies in greater detail in my book] However, protein restriction comes with a higher risk of muscle loss (sarcopenia), brittle bones, and frailty in later life.
I’m convinced that a diet high in animal protein is the better path to great health and longevity. The evidence and logic for this approach is compelling. Intermittently triggering mTOR with resistance training and high-quality animal protein while inhibiting mTOR with overnight fasting (and preferably time-restricted eating as well) seems to be a sensible approach that provides the best of both worlds. The consequences of being undermuscled cannot be overstated. Maintaining full functionality throughout life and evading sarcopenia and osteoporosis is vital. Weakness in older adults is linked to greater risk of acute health events and early death. Furthermore, having more quality muscle mass may the best thing you can do for metabolic health. Since muscle is the body’s major glucose sink that maintains healthy blood sugar levels, it may be the difference between having diabetes and not having diabetes. Once you have diabetes, your risk for cancer, heart disease, and Alzheimer’s disease increases significantly.
Do you have a different viewpoint? Please feel free to comment.