Serotonin is a funny one.
Although the prevailing sentiment is that we want to “increase serotonin,” it’s not that simple. There’s no indication that more serotonin is necessarily better in every situation, or even generally. The link between serotonin and “happiness” or “mood” isn’t so clear-cut as the experts would have you believe, either. So while I am going to tell you how to “boost” serotonin levels because serotonin is a vital neurotransmitter, I plan on sticking to foods, supplements, and behaviors that promote physiological levels of serotonin. Boosting serotonin beyond what the body is designed for may not help you, and it may have unpleasant and unwanted effects.
Is Serotonin a Mood Booster?
Yes and no. For evidence, I submit two items. The first is clinical research and the second is pure anecdote, albeit personal anecdote.
Everyone has heard of SSRIs, or selective serotonin re-uptake inhibitors. The most common form of antidepressants, their purported mode of action is to reduce the re-absorption of serotonin by neurons which increases the circulating concentration of serotonin in the brain. They increase brain levels of serotonin so it’s able to act longer. The evidence in favor of SSRIs in treating depression is mixed. Not everyone benefits, and it often takes several months to take effect. But they do help some people.
In recent years, depression studies have pitted SSRIs against another drug—tianeptine—that does the opposite: increases the absorption of serotonin by neurons and decreases the concentration of serotonin the brain. If the “serotonin=happy” hypothesis is correct, tianeptine shouldn’t improve depression. It should worsen it. But that’s not what happens. Both tianeptine, which lowers brain serotonin, and SSRIs, which increase it, have been shown to improve depression symptoms in patients with clinical depression. If anything, tianeptine might even be more effective.https://www.ncbi.nlm.nih.gov/pubmed/26805875‘>2 Adequate levels of serotonin help us deal with stress, while chronic stress can deplete serotonin. As the precursor to melatonin, serotonin also has a powerful effect on sleep and circadian rhythm.
The underrecognized effect of serotonin on the brain’s ability to learn may explain why increasing serotonin levels through SSRIs can help depression patients.https://www.ncbi.nlm.nih.gov/pubmed/11051338/‘>4 Gut serotonin may also travel to the brain via the vagus nerve, the “highway” that allows our gut to interface with our brain.
Serotonin also has other peripheral effects. For instance, it plays a role in bone formation and maintenance, with brain serotonin maintaining bone formation and gut serotonin inhibiting it.
How to Increase Serotonin
While you don’t necessarily want to boost serotonin to supernatural levels, it’s quite clear that low brain serotonin can have some unwanted effects. How do you make sure you’re making enough serotonin in your brain to enable optimal neuronal communication and melatonin synthesis, minimize rumination, and improve mood?
- Eat tryptophan foods
- Get plenty of natural light
- Get sun or take vitamin D
- Eat seafood or take omega-3s
- Spend time in nature
- Eat some carbs
- Take curcumin
- Drink coffee
- Get a massage
- Get your micronutrients
- Take tryptophan on an empty stomach
Eat Tryptophan Foods
We often forget that “thoughts” and “feelings” aren’t just ephemera floating around inside our heads without a material representative. Every thought, feeling, emotion, or mood we experience is a physical thing made of matter. We don’t just “feel better.” To feel better, we manufacture serotonin using an amino acid called tryptophan as the precursor.
Whether it’s turkey, eggs, dairy, beef, lamb, chicken, or fish, animal protein is a reliable source of tryptophan. Studies show that whey protein and egg protein both acutely increase tryptophan availability in the brain.https://www.ncbi.nlm.nih.gov/pubmed/18648776‘>6
Get Plenty of Natural Light
Sunlight is a direct trigger of serotonin synthesis. The brighter the sunlight, the higher the serotonin production.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728098/‘>8https://www.ncbi.nlm.nih.gov/pubmed/24558199‘>10
I recommend getting most of your vitamin D from the sun. It’s better regulated that way, and you get the added benefit of lots of natural light. If you need or want to supplement (probably a good idea for most people during the colder seasons when sun exposure is low), look for a high potency formula. Here’s what I take.
Eat Seafood or Take Omega-3s
Not only does seafood provide ample amounts of the amino acid tryptophan, the long-chain omega-3 fatty acids found in marine fat increase serotonin production in the brain and improve serotonin transport across neurons.https://www.ncbi.nlm.nih.gov/pubmed/27723543‘>12 Turns out that turmeric (or curcumin, rather) increases brain serotonin levels in a dose-dependent matter.https://www.ncbi.nlm.nih.gov/pubmed/2419509‘>14 This is probably why going for a walk or grabbing a quick workout is a surefire way to beat ruminating thoughts.
Generic alternative health gurus will tell you caffeine depletes serotonin. It sounds right, doesn’t it? What they won’t say is that caffeine has actually been shown to increase brain serotonin, at least in rats.https://www.ncbi.nlm.nih.gov/pubmed/16162447‘>16
Get Your Micronutrients
This should really be standard advice for any health issue. Many problems go away when we eat more micronutrients—vitamins, minerals, and phytonutrients—because micronutrients are essential to fundamental physiological processes and pathways. It’s a safe bet that all of us are at least mildly deficient in a handful of important nutrients—like B6, which regulates serotonin synthesis.https://journals.physiology.org/doi/full/10.1152/ajpendo.00582.2003‘>1 It also activates reward centers in your brain so that food is more appealing, and your motivation to eat is stronger.https://pubmed.ncbi.nlm.nih.gov/15001628/‘>3 and more strongly in response to eating carbs and protein, compared to fat.https://www.ncbi.nlm.nih.gov/pubmed/11788653‘>5 On the flip side, individuals with anorexia or cachexia due to chronic illness, who are in a severe state of negative energy balance, have high circulating ghrelin levels.https://pubmed.ncbi.nlm.nih.gov/17498507/‘>7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049314/‘>9
- Stimulating growth hormone release, which among other things helps regulate blood glucose levels during prolonged fasting or starvationhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296868/‘>11 https://academic.oup.com/jcem/article/82/11/3647/2865985‘>13 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1642692/‘>15
NPY acts to maintain energy homeostasis by decreasing energy expenditure, movement, sex drive, and thermogenesis when needed.https://www.nature.com/articles/nm1611‘>17
Another potentially exciting area of research is examining the role of NPY in aging. NPY is important for coping with and adapting to stress,https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668104/‘>19 I’m keeping my eye on this.
Peptide YY (PYY) is produced in the intestines after you eat. It travels through the bloodstream to the hypothalamus, where it inhibits NPY, decreasing appetite. PYY also modulates other digestive functions, including pancreatic and gallbladder activity.
The amount of PYY produced is proportional to the number of calories consumed. Studies find that higher-protein meals cause the greatest rise in PYY, followed by higher-fat meals. Not only do high-carb meals stimulate the least PYY, PYY peaks and then starts to decrease quickly after high-carb meals, whereas it continues to rise for hours after meals containing more fat and protein.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638054/‘>21 High levels of CCK are related to anxiety and panic attacks, while schizophrenic patients may have abnormally low levels of CCK in their brains.https://pubmed.ncbi.nlm.nih.gov/12475787/‘>23 GLP-1 figures prominently in experimental treatments for type 2 diabetes.
Following bariatric surgery, patients’ GLP-1 and PYY increase significantly, which probably accounts for post-surgical reductions in appetite,https://pubmed.ncbi.nlm.nih.gov/9152741/‘>25 Research using a rat model also suggests that GLP-1 facilitates the rapid metabolic improvements that often follow surgery.https://academic.oup.com/jcem/article/92/10/4052/2598628‘>27 Protein is also quite satiating, likely due to the actions of hormones like ghrelin and PYY.http://www.ncbi.nlm.nih.gov/pubmed?term=RHEB-1‘>1
One study (full PDF) from the 1940s found that varying amounts of twenty-four hour IFs (every other day, every fourth day, every eighth day, etc) prolonged the lifespan of rats without retarding or stunting the growth (as occurred with calorie restricting them). Female rats responded best to every eight day fasts, while males responded best to every other day fasts.
Reductions in brain insulin signaling have been shown to increase lifespan in animals, either by calorie restricting or actively knocking out brain insulin receptors.http://www.ncbi.nlm.nih.gov/pubmed/21244426‘>3
Going in and pharmaceutically manhandling your cholesterol synthesizing equipment is one thing; eating real food and exercising, resulting in possible alterations to your lipid profile, is another. We don’t set out to force your blood lipids into submission, but lifestyle changes that happen to change them for “the better” are usually a good thing. Fasting brings potent changes to blood lipids in an “organic” way – you’re just letting your machinery do its thing on its own – and this is probably a very good thing.
Intermittent fasting is as effective or even more effective than calorie restriction in improving metabolic syndrome markers in overweight women, and it’s a whole lot easier to stick with.http://www.ncbi.nlm.nih.gov/pubmed/20300080‘>5
I discussed this last week, but it can’t hurt to mention that short-term alternate day fasting wrought improvements in LDL particle size and distribution in obese adults.http://www.ncbi.nlm.nih.gov/pubmed/20815899‘>7
Heck, intermittent fasting even helped cocaine addicts stick to their treatment and rehab program.http://www.ncbi.nlm.nih.gov/pubmed/18184721‘>9 In fact, here’s a review of most of the animal anti-cancer evidence.http://www.ncbi.nlm.nih.gov/pubmed/19135806‘>11 This is refreshing news. A preliminary studyhttp://ajpregu.physiology.org/content/296/1/R29.full‘>13 I’ve found this to be the case for me. If the body “needs” food right after a workout, why would hunger be blunted? This is why I tend to hold off on the eating post-workout. Every little bit helps, especially as you age.
Fasting doesn’t cause your brain tissue to waste away, contrary to what some people will tell you. It’s actually good for brain health. Any dietary restriction tends to increase neuronal plasticity and promote neurogenesis, but it was IF that had the greatest effect (with the fewest downsides).http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.01586.x/full‘>15 That is, mice who ate larger meals more infrequently saw greater increases in brain and overall bodily health. Still another study found that IF was beneficial for peripheral nerve function in mice by promoting the maintenance of the neuronal pathways responsible for locomotor performance.http://www.ncbi.nlm.nih.gov/pubmed/21106691‘>17), which is the process by which cells recycle waste material, eliminate or downregulate wasteful processes, and repair themselves. Why is autophagy so important? It’s required to maintain muscle masshttp://www.ncbi.nlm.nih.gov/pubmed/20104028‘>19 It reduces the negative effects of aginghttp://www.ncbi.nlm.nih.gov/pubmed/17934054‘>21
Without the autophagy that fasting provides, you would get very few of the benefits. Fasting even increases neuronal autophagy,http://www.ncbi.nlm.nih.gov/pubmed/21051570‘>23 (which mean better performance down the line), improved muscle protein synthesis,http://www.ncbi.nlm.nih.gov/pubmed/20187284‘>25 (you’ll earn your meal and make more muscle out of it if you train on an empty stomach). Studies on Muslim athletes during Ramadan show no effect on performance while fasting,http://www.ncbi.nlm.nih.gov/pubmed/19787180‘>27 in those who exercise and fast rather than just fast. When you train in a fasted state, glycogen breakdown is blunted28 and more fat is burned, leaving you more glycolytic energy in the tank for when you really need it and less body fat. Those are just a sampling of the benefits to fasted training; there are dozens more.
Mental Well-being and Clarity
A lot of health influencers will tell you that failure to eat something every few hours will cause mental fog and sluggishness, so keep a banana or a granola bar on your person at all times. Of course, this is all based on an assumption that we need to supply exogenous carbs on a regular basis to properly fuel the brain. This notion that fasting is only the province of anorexics or “caveman” has kept many people from experiencing the vast array of benefits.
I maintain that one’s comfort in handling intermittent fasting effortlessly does increase dramatically when you’ve reprogrammed those cells (and genes) to predispose your body to derive most of your day-to-day energy from fat, as opposed to constantly dipping into glycogen stores (as happens when we rely so much on refeeding carbs every few hours).
Overall, fasting just seems right. It’s like a reset button for your entire body, presumably across a large spectrum of maladies and dysfunctions. It puts your body into repair mode – at the cellular level – and it can restore normal hormonal function in the obese or overweight. Now, you don’t have to fast, but it’s definitely something to consider.
Have you tried intermittent fasting yet? Let me know how intermittent fasting has worked – or hasn’t – with your lifestyle in the comment section!
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The treatment usually prescribed by doctors, hormone therapy (HT), is controversial and not appropriate for some women. I won’t get into the HT debate here—Mark did a great job covering the pros and cons recently. Suffice it to say that HT isn’t the answer for everyone, and it’s not a panacea by any means.
Whether or not they choose to go the HT route, many women desire additional support during perimenopause and beyond. For the sake of keeping this post from becoming a novella, I’m going to focus on mind-body therapies today.
This is not meant to be an exhaustive list of nonhormonal options, nor is it meant to try to dissuade you from trying HT. That’s a decision you have to make for yourself with your doctor. The approaches below can be used alone or in combination with other modalities, including HT.
As with any medical-adjacent tools, if you are considering any of the options here, take the time to educate yourself, talk to your doctor, and find qualified practitioners to help you implement these practices.
A Note Regarding Research Evidence…
Because so many women are interested in complementary or alternative approaches, there’s a fair amount of research into nonhormonal treatments. There are also important limitations.
A lot of the randomized control trials—experiments that are best for establishing causal effects—are small. There is considerable variability in research design, so it’s difficult to generalize across studies.
Participants in these studies tend to be white and well-educated. Since there are cross-cultural differences in the experience of menopause, we shouldn’t assume that the findings apply to all women. Likewise, a lot of the research focuses on women with a history of breast cancer because HT is generally contraindicated in this population. While the results of these studies probably generalize to other women, it would be great to have more data.
Finally, vasomotor symptoms—hot flushes and night sweats—are studied more than other types of symptoms. Though they are the most common complaint, many women do not experience debilitating vasomotor symptoms. They might, however, experience mood fluctuations, depression, sexual issues, memory problems, and more. We know less about how these approaches might help those women.
Nevertheless, I’ll highlight some of the potentially fruitful avenues you might explore. When possible, I’ll focus on systematic reviews and meta-analyses. They pool the results of multiple smaller studies to help a more reliable picture emerge.
Cognitive Behavioral Therapy (CBT)
In CBT, individuals are encouraged to explore how their thoughts (cognitions) affect feelings, behaviors, and physical symptoms. With help, they change their thoughts or beliefs about a situation to help manage their responses and improve coping skills.
Although there isn’t a ton of research on CBT for menopause, available studies are very promising. Whether or not CBT reduces the actual number of hot flushes—and the data here are mixed—CBT should work by changing women’s perceptions of their hot flushes. Multiple studies do find that after CBT women view their hot flushes as interfering less with daily life. As expected, they are also less bothered by them.
Women who see themselves as having less control over their hot flushes also tend to experience more distress. Changing their perceived control could be an effective intervention for improving quality of life. Indeed, in one study, 95 women received either group-based or self-help CBT. After therapy they reported feeling greater control over hot flushes and having better coping skills compared to women in a no-CBT control condition. Further analyses showed that women’s beliefs about control and coping predicted how problematic they found their hot flushes to be. (Having more positive beliefs about how hot flushes affect sleep also helped.)
Women who participated in CBT also experienced fewer sleep issues and insomnia as well as fewer depressive symptoms and sexual concerns. They also noticed less impairment at work. Positive results were found with in-person therapy, self-help programs, and telephone-based therapy. When studies included a follow-up assessment, the beneficial effects of CBT persisted for at least six months.
Mindfulness, Meditation and Relaxation Training
A cross-sectional study of 1744 women found that women with higher scores on a mindfulness assessment tended to report less severe menopausal symptoms. For women with higher life stress, this association was especially strong. The idea here is that when women are able to be present-focused and observe their symptoms without judgment, they are protected against some of the distress, and possibly the physical symptoms, associated with menopause.
Although some of the women in that survey are probably mindful by nature—lucky them—mindfulness is also a skill that can be learned and cultivated. Among the many reasons to do so, mindfulness and meditation training can apparently lessen menopausal symptoms.
For example, researchers assigned 110 women to either an intensive eight-week mindfulness-based stress reduction program or a control group. The women who received mindfulness training reported having less bothersome hot flushes, better sleep quality, less anxiety and stress, and greater overall quality of life compared to the control group. When the researchers followed participants over the next 11 weeks, these results persisted or became even stronger.
A few other studies found that women who receive mindfulness or meditation training report fewer and less bothersome hot flushes, improved sleep, and better psychological functioning, though the results have not consistently endured over time. However, when looking at more general relaxation training and paced breathing techniques, effects are minimal, at least for hot flushes.
An ethnographic study of nine female yogi masters concluded that they tend to skate fairly easily through menopause. The authors concluded that menopausal women should be encouraged to practice yoga. Of course, in addition to yoga, these yogi masters’ lifestyles included “healthy food habits, adequate sleep, and the use of nature cure techniques (i.e., fasting, detoxification, selection of suitable food products, and living in well-ventilated houses) that facilitated the art of living in tune with nature.” This sounds pretty great, but can we give really yoga all the credit here?
Probably not. However, two recent meta-analyses did conclude that yoga offers small but significant relief from symptoms of all types: vasomotor, psychological (including depression), somatic (including fatigue and sleep disturbances), and urogenital. Women also report better overall well-being and quality of life after receiving yoga training.
In one study, a group of breast cancer survivors received twelve weeks of yoga and meditation instruction, and they were encouraged to practice daily at home. Compared to women in a control group (no instruction), they reported fewer symptoms and improved quality of life at the end of the twelve weeks and again when asked three months later. A later analysis found that many of the effects were mediated by improved self-esteem in the yoga group.
Note that most of the individual studies are small, and they employ different types of yoga practices. This might be considered a strength insofar as different practices have been shown to work, or a weakness in that it’s not clear if one approach is particularly effective.
Cross-cultural surveys find that women who are more active tend to have an easier time with menopause. For example, two large surveys of Swedish women found that women who exercised at least once per week reported less intrusive symptoms than women who never exercised, and women who exercised more than three hours per week were significantly less likely to experience severe symptoms than their less active counterparts. Sedentary women in this Finnish study experienced more vasomotor, psychological, and somatic/pain symptoms than women who were at least somewhat active.
While promising, experimental studies have not yielded such favorable results. When women were assigned to “physical activity” conditions (often walking), some studies report improvements, but others find no improvements or even worsening symptoms (perhaps depending on women’s baseline fitness). Multiple reviews have concluded that there is no systematic effect of exercise, particularly not for vasomotor symptoms.
Does that mean menopausal women shouldn’t exercise? Obviously no. It’s clear that being active—or at least not being sedentary—is important for overall health, and it probably helps menopausal women through the transition. However, there isn’t enough research to know what types of exercise are most effective and when. Do the types of movement you enjoy and that make your body feel good.
A recent review concluded that acupuncture is effective for reducing vasomotor symptoms, both frequency and severity, as well as for improving quality of life. However, the reviewers also found that acupuncture was not reliably better than sham acupuncture where needles are inserted at points other than the prescribed pressure points and at a shallower depth—a placebo condition.
A handful of studies have shown that clinical hypnosis can reduce hot flush frequency and distress among breast cancer patients. Another study of 187 women without breast cancer found that women who received hypnotherapy had fewer, less severe, and less bothersome hot flashes, as well as improved sleep. These results were evident at the end of the five-week treatment protocol, and they remained or got stronger in the six-week follow-up period.
The Experts Weigh In…
In 2015, the North American Menopause Society released a position statement on nonhormonal management of vasomotor symptoms. Of the approaches discussed here, the only ones NAMS recommended based on the strength of the available evidence were CBT and hypnosis. Mindfulness-based stress reduction earned a “recommend with caution,” which means, “We think it might work, but the evidence isn’t conclusive.”
The others—yoga, exercise, relaxation and paced breathing techniques, and acupuncture—were not recommended. This does not mean they are not worth trying! It simply means that based on their standards, the evidence was not strong enough for the committee to conclude that they are likely to be effective treatments for vasomotor symptoms specifically. This says nothing about other types of symptoms, nor about general well-being or quality of life.
Mind-Body Therapy Pros and Cons
So where does this leave us? Each of these therapies shows promise for alleviating at least some symptoms of menopause. Moreover, all these therapies have the potential to improve overall quality of life, sleep, stress, and general health. While reading these studies, I did wonder whether some of the women felt better simply because they were investing time and energy in taking care of themselves. If so, is that a problem? I don’t think so. They are low-risk interventions with a lot of potential upside.
That said, these aren’t quick solutions. The effective mindfulness/mediation trainings included six to eight weeks of classes and multiple hours per week. Women practiced yoga for two to four months during the study periods. Hypnotherapy was five weeks or longer. It’s not clear what the minimum time frame is for each of these therapies to be useful, but they’ll certainly involve a time commitment that might not be practical for all women. However, yoga, mindfulness/meditation, exercise, and even CBT can all be practiced at home once you know the proper technique.
As I said at the beginning, this is not an exhaustive list of nonhormonal therapies. There are also various supplements that might help, as well as lifestyle modifications that most of you Primal-savvy readers are probably already implementing: eating a variety of nutrient-dense foods, getting plenty of sunlight, practicing good sleep hygiene, and nurturing social connections.
Whatever you choose, be patient. Don’t just focus on one symptom; focus on the big picture. Pay attention to how you’re feeling more globally. Consider that while an intervention might not hit its desired mark, it might help you in ways you didn’t expect.
Have you used mind-body techniques (these or others)? What’s been your experience? Share your insights and questions below, and have a great week, everyone.
Atapattu PM. Vasomotor symptoms: What is the impact of physical exercise? J SAFOMS. 2105 Jan-Jun;3(1):15-19.
Goldstein KM, et al. Use of mindfulness, meditation and relaxation to treat vasomotor symptoms. Climacteric. 2017 Apr;20(2):178-182.
McMillan TL, Mark S. Complementary and alternative medicine and physical activity for menopausal symptoms. J Am Med Womens Assoc (1972). 2004 Fall;59(4):270-7.
Molefi-Youri W. Is there a role for mindfulness-based interventions (here defined as MBCT and MBSR) in facilitating optimal psychological adjustment in the menopause? Post Reprod Health. 2019 Sep;25(3):143-149
Moore TR, Franks RB, Fox C. Review of Efficacy of Complementary and Alternative Medicine Treatments for Menopausal Symptoms. J Midwifery Womens Health. 2017 May;62(3):286-297.
Sliwinski JR, Johnson AK, Elkins GR. Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind-Body Medicine to Improve Cognitive Performance. Integr Med Insights. 2014;9:17–23.
van Driel CM, Stuursma A, Schroevers MJ, Mourits MJ, de Bock GH. Mindfulness, cognitive behavioural and behaviour-based therapy for natural and treatment-induced menopausal symptoms: a systematic review and meta-analysis. BJOG. 2019;126(3):330–339.
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Inflammation gets a bad rap in the alternative health world: “Inflammation causes heart disease, cancer, and autoimmune disease! It’s at the root of depression.” These are all true—to some extent.
Name a disease, and inflammation is involved.
Crohn’s disease is inflammatory.
Major depression is inflammatory.
Heart disease is inflammatory.
Autoimmune diseases, which involve an inflammatory response directed at your own tissues, are inflammatory.
Arthritis is inflammatory.
Even obesity is inflammatory, with fat cells literally secreting inflammatory cytokines.
Yes, but the story is more complicated than that. Inflammation, after all, is a natural process developed through millions of years of evolution. It can’t be wholly negative. Just like our bodies didn’t evolve to manufacture cholesterol to give us heart disease, inflammation isn’t there to give us degenerative diseases.
So, Why Does Inflammation Happen?
When pain, injury, or illness hit, the first responder is the acute inflammatory response. In other words, it is brief, lasting several days or less. All sorts of things can cause an acute inflammatory response. Here are a few:
- Trauma (punch, kick, golf ball to the head)
- Infection by pathogens (bacterial, viral)
- Burn (sun, fire, seat belt buckle on a summer day)
- Chemical irritants
- Allergic reaction
Things happen pretty fast in an acute inflammatory response and involve several different players, including the vascular system (veins, arteries, capillaries and such), the immune system, and the cells local to the injury.
- First, something painful and unpleasant happens; choose one of the above injury options.
- Then, pattern recognition receptors (PRR) located at the injury site initiate the release of various inflammatory mediators, which in turn initiate vasodilation (or widening of the blood vessels). This allows increased blood flow to the injury site, which warms the site, turns it the familiar red, and carries plasma and leukocytes to the site of the injured tissue.
- The blood vessels become more permeable, thus allowing the plasma and leukocytes to flow through the vessel walls and into the injured tissue to do their work. Emigration of plasma into tissue also means fluid buildup, which means swelling.
- At the same time, the body releases an inflammatory mediator called bradykinin, which increases pain sensitivity at the site and discourages usage of the injured area. These sensations—heat, redness, swelling, pain, and a loss of function—are annoying and familiar, but they’re absolutely necessary for proper healing.
Why Is (Acute) Inflammation Essential?
Allow me to explain why the four primary symptoms of acute inflammation are necessary, despite being unpleasant:
- Increased blood flow warms the injury and turns it red, which can be irritating and unsightly, but it also carries the guys—leukocytes—that will be cleaning up the injury site, mopping up pathogens, and overseeing the inflammatory process.
- Swollen body parts don’t fit into gloves, are really sensitive, and don’t work as well as their slim counterparts, but a swollen finger is a finger that’s full of a plasma and leukocyte slurry and therefore on the road to recovery.
- Pain hurts, but if an injury doesn’t hurt and it’s serious, you’ll keep damaging it because you won’t know not to use it.
- Loss of function prevents you from using what could be one of your favorite body parts, but you don’t want to make it worse be re-injuring it. Besides, it’s only temporary.
What About Chronic Inflammation?
These symptoms both indicate and enable inflammation (and, thus, healing), but what’s the deal with inflammation being linked with all those chronic illnesses—like obesity, heart disease, and depression? How does something normal and helpful go haywire and become implicated in some of the most crushing, tragic diseases of our time?
When inflammation becomes chronic and systemic, when it ceases to be an acute response, when it becomes a constant low-level feature of your physiology that’s always on and always engaged, the big problems arise.
The inflammatory response is supposed to be short and to the point. And because a big part of inflammation is breaking the tissue down, targeting damaged tissue and invading pathogens, before building it back up, the inflammatory response has the potential to damage the body. That’s why it’s normally a tightly regulated system: because we don’t want it getting out of hand and targeting healthy tissue. But if it’s on all the time—if chronic inflammation sets in—regulation becomes a lot harder.
Acute vs. Chronic Inflammation
A perfect example of the acute inflammation versus chronic inflammation dichotomy is exercise.
A single hard workout raises inflammation. It’s a stressor, a damaging event imposed upon your body. See for yourself.
A hard run spikes C-reactive protein for up to two days.
During exercise, skeletal muscle releases the inflammatory cytokine IL-6, a marker of damage.
Volleyball practice elicits spikes in IL-6 in both male and female elite volleyball players.
Acute exercise spiked CRP in cardiovascular disease patients (but a four-month exercise program lowered it).
This table of inflammatory responses to strenuous endurance events shows some massive spikes in CRP, some up to 20-fold the baseline value.
Yet, study after study (epidemiological and clinical alike) shows that extended exercise programs generally reduce markers of inflammation (like C-reactive protein) over the long-term:
- In elderly Japanese women, a 12-week resistance training program reduced circulating levels of inflammatory markers compared to baseline; reductions in CRP were associated with increases in muscle thickness.
- American adults who engaged in frequent physical activity tended to have lower CRPs than adults who were more sedentary.
- In type 2 diabetics, (key term coming up) long-term high intensity resistance and aerobic training reduced inflammatory markers over the course of a year (independent of changes in body weight, meaning activity was the key factor).
- Endurance combined with resistance training reduced CRP in young, healthy women better than endurance training alone.
- In obese, post-menopausal women, a basic moderate cardio program lowered CRP without really affecting body weight either way over the course of a year.
There are many more out there, but the general gist is that regular exercise tends to lower markers of systemic inflammation while acute exercise increases markers of acute inflammation. And sometimes what’s acute can become chronic. How do we make sense of this? How do we avoid making those acute spikes a chronic, constant thing?
Identifying Chronic Inflammation: Objective Markers
First, we need to be able to identify chronic inflammation. What symptoms and biomarkers can we use to track our inflammation levels?
CRP, or C-Reactive Protein
CRP is a protein that binds with dead and dying cells and bacteria in order to clear them from the body. It can always be found (and measured) in the bloodstream, but levels spike when inflammation is at hand. During acute inflammation caused by infection, for example, CRP can spike by up to 50,000-fold. CRP spikes due to acute inflammation peak at around 48 hours and declines pretty quickly thereafter (post acute-phase inflammation CRP has a half life of 18 hours). Thus, if the incident causing the inflammation is resolved, CRP goes back to normal within a few days. If it persists, the infection/trauma/etc. probably persists as well.
Highly sensitive to many different kinds of stressors, CRP rises in response to essentially anything that causes inflammation. This makes it valuable for determining that inflammation is occurring, but it makes it difficult to determine why that inflammation is occurring—because it could be almost anything. But if you’re looking for confirmation that you are chronically, systemically inflamed, an elevated CRP (in absence of any acute infections, injuries, burns, or stressors) is a useful barometer.
“Normal” CRP levels are supposedly 10 mg/L. Absent infection or acute stressors, however, ideal CRP levels are well under 1 mg/L. You want to stay well below 1; you don’t want “normal.” Between 10-40 mg/L (and perhaps even 1-9 mg/L, too) indicates systemic inflammation (or pregnancy), while anything above that is associated with real acute stuff. Note that exercise can elevate CRP, so don’t get tested if you’ve worked out in the last couple days.
IL-6, or Interleukin-6
T cells (type of white blood cell that plays a huge role in the immune response) and macrophages (cells that engulf and digest—also known as phagocytosing—stray tissue and pathogens) both secrete IL-6 as part of the inflammatory response, so elevated IL-6 can indicate systemic inflammation.
Tissue Omega-3 Content
This is a direct measurement of the omega-3 content of your bodily tissue. It’s not widely available, but it is very useful. Remember that anti-inflammatory eicosanoids draw upon the omega-3 fats in your tissues and that inflammatory eicosanoids draw upon the omega-6 fats. People having a higher proportion of omega-6 fats will thus produce more inflammatory eicosanoids. Now, we absolutely need both inflammatory and anti-inflammatory eicosanoids for proper inflammatory responses, but people with high omega-6 tissue levels make way too many inflammatory eicosanoids. Studies indicate that people with the highest omega-3 tissue levels suffer fewer inflammatory diseases (like coronary heart disease).
Research (highlighted and explicated here by Chris Kresser) suggests that omega-3 tissue concentrations of around 60% are ideal, which is a level commonly seen in Japan—the seemingly paradoxical land of high blood pressure, heavy smoking, and low coronary heart disease rates.
This measures the EPA and DHA, the two important omega-3 fatty acids, as a percentage of total fatty acids present in your red blood cells. It doesn’t correlate exactly to tissue amounts, but it’s pretty good and a powerful predictor of cardiovascular disease risk. The omega-3 index doesn’t measure omega-6 content, but those with a low omega-3 index are probably sporting excessive omega-6 in their red blood cells.
Anything above 8% corresponds to a “low risk,” but levels of 12-15% are ideal and roughly correspond to the 60% tissue content mentioned by Chris’ article. Four percent and below is higher risk and can be viewed as a proxy for increased inflammation (or at least the risk of harmful systemic inflammation developing from normal inflammation).
Heart Rate Variability
Systemic Inflammatory Response Syndrome Score
There’s the systemic inflammatory response syndrome, which is incredibly serious and has four criteria. If you have two or more of them at once, congratulations: you qualify—and should probably see a health professional immediately. This isn’t relevant for low-grade systemic inflammation, like the kind associated with obesity or autoimmune disease.
- Body temperature less than 96.8 F (36 C) or greater than 100.4 F (38 C).
- Heart rate above 90 beats per minute.
- High respiratory rate, 20 breaths per minute or higher.
- White blood cell count fewer than 4000 cells/mm³ or greater than 12,000 cells/mm³.
Of these objective markers to test, I’d lean toward CRP, HRV, and one of the omega-3 tests. CRP is pretty comprehensive, HRV is a two-fer (inflammation and general stress/recovery), and, while omega-3 tissue or blood cell content doesn’t necessarily indicate the existence of systemic inflammation in your body, it does indicate the severity of the inflammatory response you can expect your body to have. Taken together, these tests will give you an idea of where you stand.
Identifying Inflammation: Subjective Markers
There are also subjective markers. They may be harmless artifacts, but they may indicate that something systemic is going on.
Flare-up of Autoimmune Conditions You Haven’t Heard From In Ages
Sore joints, dry, patchy, and/or red skin, and anything else that indicates a flare-up. For me, this is usually mild arthritis.
Acute inflammation is often characterized by swelling at the site of injury. The same effect seems to occur in states of systemic inflammation, although they aren’t localized, but rather generalized.
If you feel stressed, you’re probably inflamed. I’m talking about the kind that has you rubbing your temples, face palming, sighing every couple minutes, and pinching the space between your eyes very, very hard.
Persistent But Unexplained Nasal Congestion
Could be allergies, sure, but I’ve always noticed that when I’m under a lot of stress and generally in an inflamed state, my nose gets clogged. Certain foods will trigger this, too, and I think it can all be linked to a persistent but subtle state of inflammation.
If you fit the bill for the eight signs of overtraining listed in this post, you’re probably inflamed.
Ultimately, though? It comes down to the simple question you must ask yourself: How do you feel?
I mean, this seems like an obvious marker, but a lot of people ignore it in pursuit of numbers. If you feel run down, lethargic, unhappy, your workouts are suffering, you struggle to get out of bed, you’re putting on a little extra weight around the waist, sex isn’t as interesting, etc., etc., etc., you may be suffering from some manner of systemic, low-grade inflammation. Conversely, if you’re full of energy, generally pleased and/or content with life, killing it in the gym, bounding out of bed, lean as ever or on your way there, and your sex drive is powerful and age appropriate (or inappropriate), you’re probably not suffering from chronic inflammation.
Causes of Chronic Inflammation
We need to determine why inflammation is “on” all the time—and then take the steps to counter it. I’m going to fire off a few things that both induce inflammation and tend toward prevalence in developed countries. You let me know if anything sounds familiar to you.
- Toxic diets: High-sugar, high-processed carb, high-industrial fat, high-gluten, high-CAFO meat, low-nutrient food is a pretty accurate descriptor of the modern Western diet.
- Insufficient omega-3 intake: Omega-3 fats form the precursors for anti-inflammatory eicosanoids, which are an integral part of the inflammatory response. Poor omega-3 status means insufficient production of anti-inflammatory eicosanoids and a lopsided inflammatory response to normal stimuli.
- Excessive omega-6 intake: Omega-6 fats form the precursors for inflammatory eicosanoids, which are an integral part of the inflammatory response. High omega-6 status (especially when combined with poor omega-3 status) means excessive production of inflammatory eicosanoids and a lopsided inflammatory response to normal stimuli. The more omega-6 you eat, the more omega-3 you crowd out for anti-inflammatory eicasonoid formation.
- Lack of sleep: Poor sleep is linked to elevated inflammatory markers. Poor sleep is a chronic problem in developed nations. Either we go to bed too late, wake up too early, or we use too many electronics late at night and disrupt the quality of what little sleep we get. Or all three at once.
- Lack of movement: People lead sedentary lives, by and large, and a lack of activity is strongly linked to systemic, low-grade inflammation. People don’t have to walk to get places, they take escalators and elevators, they sit for hours on end, and they don’t have time for regular exercise.
- Poor recovery: Other people move too much, with too little rest and recovery. When I ran 100+ miles a week, I certainly wasn’t sedentary, but I was chronically inflamed. Overtraining is a form of chronic inflammation.
- Chronic stress: Modern life is stressful. Bills, work, commuting, politics, exercise that you hate – it all adds up and it doesn’t seem to let up or go away. And if it becomes too much for you to handle (I know it’s too much for me at times), your body will have a physiological, inflammatory response to emotional stress.
- Lack of down time: When you’re always on the computer, always checking your email/Facebook/smartphone, you are always “on.” You may think you’re relaxing because your body is stationary, but you’re not relaxing.
- Lack of nature time: We spend too much time contained in cubicles, cars, trains, and cities, away from trees, leaves, and soft earth. In a way, nature is home for us. Going home certainly has its measured benefits.
- Poor gut health: The gut houses the bulk of the human immune system. When it’s unhealthy, so is your inflammatory regulation. A healthy gut is also selectively permeable, allowing beneficial compounds passage into the body and keeping toxins out. An unhealthy gut often becomes leaky, allowing toxins into the body to stimulate an immune, inflammatory response.
- Poor acute stressor/chronic stress ratio: We respond far better to acute stressors than repeated, sustained stress – even if the latter is of a lower intensity.
See what I mean? Since we’re set up for acute stressors requiring an acute inflammatory response, all this other low-level, evolutionarily-discordant, superficially mild stuff set against a backdrop of misaligned fatty acid ratios and impaired gut health throws us off and sets us up for a lifetime of chronic inflammation.
Inflammation is a complex physiological process that can go wrong in a lot of ways. But luckily, sticking to the tried and true dietary and lifestyle measures will get you most of the way toward preventing inflammation from becoming chronic and untamed.
If you have any further questions about inflammation, fire away down below! Thanks for reading.
Eliakim A, Portal S, Zadik Z, et al. The effect of a volleyball practice on anabolic hormones and inflammatory markers in elite male and female adolescent players. J Strength Cond Res. 2009;23(5):1553-9.
Lara fernandes J, Serrano CV, Toledo F, et al. Acute and chronic effects of exercise on inflammatory markers and B-type natriuretic peptide in patients with coronary artery disease. Clin Res Cardiol. 2011;100(1):77-84.
Ford ES. Does exercise reduce inflammation? Physical activity and C-reactive protein among U.S. adults. Epidemiology. 2002;13(5):561-8.
Balducci S, Zanuso S, Nicolucci A, et al. Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutr Metab Cardiovasc Dis. 2010;20(8):608-17.
Daray LA, Henagan TM, Zanovec M, et al. Endurance and resistance training lowers C-reactive protein in young, healthy females. Appl Physiol Nutr Metab. 2011;36(5):660-70.
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The ketogenic diet has exploded in popularity over the last few years. Hordes of people are using it to lose body fat, overcome metabolic diseases, improve their endurance performance, attain steady energy levels, make their brain work better, and control seizures. And increasing numbers of researchers and personal experimenters are even exploring the utility of ketogenic diets in preventing and/or treating cancer. After all, back in the early part of the 20th century, Warburg discovered an important characteristic of most cancer cells: they generate their energy by burning glucose. If a particular cancer loves glucose, what happens if you reduce its presence in your body and start burning fat and ketones instead?
It’s taken a while, but the research community is finally beginning to take a few swings at this and similar questions.
So, what do we know?
First, let’s just go through a few recent human studies and case studies.
Keto and Cancer Treatment
Women with endometrial or ovarian cancer improved energy levels, appetite, and physical function on a ketogenic diet.
A Bayesian approach to studying the effects of ketogenic diets in humans and animals with high grade glioma (a brain cancer) found an “overall survival-prolonging effect.”
In gliomas, an analysis of available case studies using ketogenic diets found increased overall or progression-free survival. These were not randomized controlled trials, however, so they say nothing definitive.
A recent review paper gives a good overview of the current state of ketogenic diet and cancer research, finding that:
- Ketosis targets tumor metabolism.
- Ketosis improves effectiveness of conventional therapies.
- Ketosis has favorable effects of anti-cancer gene expression.
One thing you might notice is that there are no studies showing that standalone ketogenic diets cure cancer. There aren’t very many randomized controlled trials in general.
What there are are studies showing that ketogenic diets are safe and potentially effective adjuvant treatments—treatments that supplement conventional cancer treatments. You don’t see keto “defeating” cancer alone. You see keto enhancing the effect of chemotherapy. You see keto enhancing the effect of radiation. You see keto protecting normal cells and increasing the vulnerability of cancer cells to conventional treatment.
That’s not to say that keto can’t beat cancer. Maybe it can. But the clinical research simply isn’t there to say one way or the other.
Where keto seems even more promising is in prevention of cancer.
Keto and Cancer Prevention
Diabetes is a disease of carbohydrate intolerance. It’s a disease in which carbohydrate consumption results in elevated blood sugar, exaggerated insulin response. The way most people with diabetes eat leads to chronically high levels of insulin and blood sugar. Yeah, yeah, I know about all the badass Primal eaters who are “technically” diabetic but keep their blood sugar pristine and insulin minimized by watching what they eat, exercising regularly, and just generally leading a healthy lifestyle—but those people aren’t a large enough a group to have an effect on the category known as (and studied as) “diabetics.” Most people with diabetes unfortunately keep eating the same junk that got them there.
What does research say about the cancer rate of most people with diabetes? It’s usually higher.
One of the most consistent risk factors for many types of cancer is having diabetes and experiencing all the metabolic fallout that entails—high fasting insulin, insulin resistance, elevated blood glucose. Cancers of the liver, pancreas, breast, endometrium, bladder, and kidney all have strong associations with type 2 diabetes. This should come as no surprise. Not only do many cancers thrive on glucose as fuel, the high insulin levels typical of people with diabetes and insulin resistance increase the availability of growth factors that promote cancer growth.
Meanwhile, therapies that are known to reduce the symptoms of diabetes—lower fasting insulin, increase insulin sensitivity, normalize blood sugar, etc—tend to lower the risk of cancer. A perfect example is metformin.
Metformin activates AMPK, the same autophagy pathway activated by exercise, fasting, polyphenol consumption, and reduced calorie intake. It lowers blood sugar, increases insulin sensitivity, and extends the lifespan of type 2 diabetics.
Metformin also seems to protect against cancer. It lowers hyperinsulinemia and may protect against insulin-related cancers (breast, colon, etc). Early treatment during adolescence, for example, protects rats against later tumor growth.
What does this have to do with ketogenic diets?
Ketogenic diets have many similar effects. They activate AMPK. They lower blood sugar. They’re great for fat and weight loss, which enhances insulin sensitivity. Recently, researchers have even used ketogenic diets to resolve type 2 diabetes.
Now, not all cancers are linked to diabetes. For example, diabetes doesn’t increase the risk of gastric cancer. That’s because it’s linked to bacterial infection, not elevated blood sugar. And that’s why taking metformin doesn’t reduce the risk of gastric cancer. This actually supports my hypothesis that, when diabetes does not increase the risk of a cancer, neither does metformin reduce it—like gastric cancer. Diabetes doesn’t increase it, so metformin doesn’t reduce it. That’s the mechanism in play.
Nor do all cancers burn glucose exclusively. Some thrive in a ketogenic environment.
There is a mutation called BRAF V600E in certain cancer cells that allows them to utilize ketone bodies to stimulate growth. About 50% of melanoma, 10% of colorectal cancer, 100% of hairy cell leukemia, and 5% of multiple myeloma cases exhibit the ketone-utilizing BRAF V600E mutation. Indeed, a cancer cell’s inability to break down and metabolize ketone bodies is the best predictor of whether a ketogenic diet can even help against a given cancer.
But if we’re talking prevention. If we accept that not developing diabetes—all else being equal— probably reduces the risk of getting cancer, then using ketosis to improve all the same symptoms linked to diabetes should also reduce the risk of getting cancer. And if it doesn’t reduce the risk, it probably won’t hurt. I mean, is there a doctor alive who claims that increasing insulin sensitivity, lowering hyperinsulinemia, and losing body fat will increase the risk of cancer?
A Few Takeaways To Consider
As I see it—and this is not medical advice—the most promising use of ketogenic diets in cancer are as follows.
Adjuvant therapy: Using ketosis to enhance the efficacy of conventional therapies like chemotherapy and radiation, increasing the susceptibility of cancer cells to treatment and increasing survival of healthy host cells.
Prevention: Using ketosis (whether intermittently or long term) to lower fasting blood glucose, reduce diabetes risk (or resolve extant diabetes), and improve your ability to burn fat and not rely on exogenous glucose so much should in theory reduce your risk of most cancers.
Whatever you do, if you’re an actual cancer patient, discuss this with your doctor. Make sure your particular variety of cancer isn’t partial to ketones. Make sure it’s one of the cancers that actually craves glucose. If you end up with a cancer that thrives on ketone bodies, and you go deep into perpetual ketosis, you could be making an enormous mistake.
But the bottom line is that, assuming you don’t already have one of the cancers known to utilize ketones, going into ketosis from time to time isn’t going to hurt—and it will probably help reduce the risk of cancer.
I’m going to close this post with an anecdote from one of my employees. His father passed away a dozen years ago from multiple myeloma, a type of white blood cell cancer. This was before he worked at Primal Nutrition; he was just getting involved in alternative forms of health and nutrition research. What struck him most, particularly in retrospect, was how his father’s appetite changed during his battle with cancer. He began craving candy—Reese’s peanut butter cups, Hershey’s kisses, Now-and-Laters, and all other kinds. As he says it, looking at his dad’s snack drawer was like looking at the archetypal bag of Halloween candy.
I don’t know if this is evidence of anything. Can cancer actually tap into your specific appetites? Can it change how you perceive and desire specific foods? Was his father actually being programmed by his cancer to over-consume sugar?
What I do know is that no one needs garbage candy. A few seconds of momentary gustatory pleasure, followed by regret and the incessant need to repeat—is it worth it? Is it worth the off chance that eating lots of sugar feeds and promotes cancer? Don’t do it, folks. I know my longtime readers are right there with me. I know you guys who’ve been here from the beginning are probably getting egged on Halloween because you’re giving out collagen packets and mini-kettlebells. But if you’re new to this site and way of eating in general—maybe a co-worker passed my info along to you, maybe you’re trying to make a big change in the way you eat and live—avoiding the obviously terrible-for-you stuff like candy and baked goods is the biggest change you can make. And not just for cancer.
So, do I want you to walk away from this post thinking that keto is a cancer cure? No. I’m a fan of ketosis, and I think almost everyone should spend time in that metabolic state, but I don’t consider it to be magical. The jury is definitely still out. Does ketosis look like a strong candidate for improving efficacy of various therapies in certain cancer patients? Yes. Can keto improve health markers shown to reduce a person’s risk of getting cancer in the first place? Yes.
The keys to good health are generally speaking pretty consistent.
- Maintain good insulin sensitivity.
- Avoid glucose intolerance.
- Get plenty of sleep.
- Consume hormetic stressors.
- Avoid obesity. Lose body fat.
- Exercise, or at least move every day.
- Dip into ketosis on a regular basis, either from ketogenic dieting, fasting, meal skipping, or (non-chronic) hard training—or all of the above.
There’s no guarantee against cancer, but I think the advice I just mentioned supports a good fighting chance.
Take care, everyone. Be well.
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