Root Causes of Vaginal Infections: Hormone Balance and the Mycobiome

Almost immediately after treating for ureaplasma, I began to experience vaginal odor that came and went erratically and was worse after sex. It sounds like a classic case of bacterial vaginosis (BV), right? Only, none of the words I read online about any kind of vaginal odor, healthy or not, seemed like the right one. I didn’t have the language to describe what I was experiencing. And so treatment after treatment, I found myself in a white, clinical emptiness between mystery and the feeling that we weren’t treating for what was wrong with me.

Vaginal pH

The first line of treatment for most women who experience vaginal odor is pH-D, a boric acid suppository that lowers the pH of your vagina by literally placing an acidic compound up there. A healthy vaginal pH is considered to fall between 3.8 and 4.5 on the pH scale. In that range, the bacteria you want to grow, lactobacilli, while a pH above 4.5 promotes growth of disruptive bacteria. The idea behind pH-D is that if you have odor, you have an overgrowth of disruptive bacteria, and returning your vagina to an acidic state will stop their growth, giving your lactobacilli a chance to take back over.

I tried boric acid many times, and sometimes it subdued the odor a little, but I can say with certainty now that boric acid DOES NOT work for my body. In the words of my former gynecologist, it “made her angry,” meaning that as I sat there in stirrups, my vagina was red and inflamed. She thought that boric acid swung the pH of my vagina too far in the acidic direction, so that as my body was naturally trying to heal itself, which it will do (it just needs time), introducing boric acid was making it go on a roller coaster that actually made normalizing the pH of the environment harder.

I’d try boric acid once many months later, after my body had healed considerably from all of the antibiotics that had damaged my collective microbiome, as a preventive measure around the time of my period. I experienced odor after taking it, along with abnormal discharge. You could say the effect was correlative, but even if it were, the correlation was enough for me to suspect that it messed with my hormones and caused my symptoms.

Antibiotics: A Conventional Approach

In September I saw another gynecologist in the same practice for an emergency visit because I thought I was developing some sort of infection. She prescribed a metronidazole gel that I used for only one night because I hated it — it made me feel inflamed — followed by a clindamycin cream for one week that felt cool when I inserted it using the applicator. She also prescribed a vaginal estrogen cream for one month, but after two weeks I stopped using it because it caused irregular bleeding.

In November I was referred to a gynecology specialist who was a World Health Organization consultant and saw a lot of complicated cases like mine. She prescribed a two-week, twice-daily dose of oral metronidazole (to which I noticed no response whatsoever) to follow with clindamycin cream again, because of its anti-inflammatory properties. The prescription was for three times per week for at least four months; I made the decision to again stop treatment two months early when I met with an Evvy health coach who planted seeds of doubt in my head that this was a good approach.

Vaginal Microbiome Testing

I’d discovered Evvy and taken my first test just in time to bring the results to my appointment. While Evvy claims that test results are to be considered informational rather than diagnostic, they did serve as an amazing source of information when I had no other leads. I, along with all of the naturopathic doctors I know, am an advocate for information in the form of labs and clinical research.

The results from my first test showed that I had an L. crispatus-dominant vaginal microbiome, which translates to a Type 1 Community State Type (CST). Surprisingly, given the number of infections I’d had, this is considered the healthiest type, the most protective against infections including UTIs as well as the lowest risk for infertility and highest success rates of assisted reproductive techniques.

Research on vaginal microbiome CSTs is budding, and every microbiome shows variation, but the CSTs offer a helpful framework for describing what’s going on with your vaginal microbiome holistically while also showing the composition of your vaginal microbiome in detail. (Evvy uses a kind of next-generation sequencing called shotgun metagenomics that sequences any and all microbial DNA present and then matches it to microorganisms via bioinformatics, so you learn everything that’s in your vaginal microbiome.)

Each of the five CSTs is characterized by the type and amount of Lactobacillus present, which exhibit different protective effects:

· Type 1: L. crispatus dominant

· Type 2: L. gasseri dominant

· Type 3: L. iners dominant

· Type 4: no Lactobacillus dominance

· Type 5: L. jensenii dominant

Evvy tests served as a decision-making tool for me. After the extended treatment with metronidazole and clindamycin, plus a round of cefuroxime for a UTI (I learned later that this is not a good antibiotic, and I would never take it again), my Type 1, 96.63% L. crispatus-dominant CST was reduced to a Type 4 CST with 90% disruptive bacteria.

To the specialist’s credit, she was knowledgeable — we had an in-depth conversation about L. crispatus — and I think she at least suspected a hormonal component to the problem, rather than assuming it was all microbial. She put me on the Nuvaring, which contains mostly localized estrogen that she thought could help to increase my lactobacilli count; she didn’t see many under the microscope. (I say mostly because nothing in your body is entirely separate from the rest of your body; at least some amount of estrogen will circulate in your bloodstream, as naturopathic doctors would educate me.)

My Evvy results, however, solidified my commitment to exploring a naturopathic approach to treatment. After working with a naturopathic doctor (ND) for two months, my microbiome was at least restored to a Type 2 state dominated by L. gasseri, but I had only 0.34% L. crispatus. I mourn the loss of my L. crispatus. Sometimes I wonder if I’ve gotten it back and think about testing with Evvy again — after learning so much about my body, I didn’t feel the need to anymore — but maybe I will, someday soon.

Naturopathic Medicine for Vaginal Infections

Everyone was trying to treat BV, an imbalance of vaginal bacteria favoring pathogenic anaerobes such as Gardnerella (the most common culprit), Atopobium vaginae (which one doctor told me grows on the scaffold created by Gardnerella biofilms), Mobiluncus, Prevotella, Streptococcus, Mycoplasma, Ureaplasma, Dialister, and Bacteroides. BV isn’t the only condition associated with vaginal dysbiosis; aerobic vaginitis (AV) is another, characterized by an overgrowth of aerobic, rather than anaerobic, disruptive bacteria. One gynecologist at one point in time did wonder if this is what I had. I never got an answer.

The problem with this type of thinking is that what I was experiencing wasn’t only microbial; it was microbial and hormonal. Naturopathic doctors, who have a deeper respect for relationships within the body, understood that.

When it comes to naturopathic medicine, I can’t emphasize enough that you have to have confidence in who you’re working with. Always consult your gut as your source of truth, or, in a way that is all too real for the context of this article, use the sniff test.

Hormone Imbalance Can Cause Vaginal Infections

My first assignment from my first ND was to take the DUTCH Complete test, which measures sex and adrenal hormones and their metabolites, along with six organic acids. This test was another beginning. Every gynecologist I have ever asked has told me that hormone tests aren’t meaningful, because they capture your levels at a single point in time, while your hormones fluctuate over your cycle — but the DUTCH test took note of where I was in my cycle and compared my levels to the normal range for that period of time.

The results showed that my levels of all three primary estrogens — estrone, estradiol, and estriol — were low, and in the case of estriol, nearing the postmenopausal range. My ND explained that in some women, use of birth control over many years can do this, because what birth control does is essentially tell your brain it doesn’t need to produce the hormones it’s replacing. With time, however, hormone balance (and fertility) can be restored.

Estrogen promotes the growth of lactobacilli by producing glycogen, which helps lactobacilli to grow. Not only does this in and of itself help to maintain a healthy vaginal microbiome, but lactobacilli produce lactic acid, which facilitates local immune response by increasing the release of interleukin (IL)-1β and IL-8 from vaginal epithelial cells. Vaginal epithelial cells only produce L-lactic acid, whereas certain types of lactobacilli (including L. crispatus, L. gasseri, and L. jensenii) produce D-lactic acid, so having those types of dominant strains can further increase the amount of lactic acid present.

The test also showed that my cortisol levels upon waking and in the morning were low, which explained why I felt so tired in the mornings. For this, my ND gave me supplements with high doses of vitamins B5, B6, and B12, which support the adrenals and energy levels and can be depleted by birth control, as well as adrenal-supportive herbs, such as rhodiola and eleuthero.

The adrenals are a part of the hypothalamic pituitary adrenal (HPA) axis (there is also a hypothalamic pituitary ovarian axis). In this way they facilitate communication between the nervous system and endocrine system, producing hormones such as cortisol and the “fight or flight” hormones adrenaline and noradrenaline. Prolonged periods of stress, such as those caused by chronic infections, can cause your adrenals to go into overdrive, or survival mode.

While the adrenals don’t make estrogen, there is a connection between stress, the reproductive axis, and fertility. And while scientists don’t seem to know why stress affects fertility, I wonder if the HPO axis has something to do with it.

Vaginal Suppositories

The findings revealed a root cause of my infections: my body didn’t have enough estrogen, and it was too stressed out to make more of it. To increase the amount of local estrogen in my vagina, I used Bezwecken ovals, the 2x strength kind, which contain estrogen and helped a lot. (Months later, to help with vaginal dryness, I would self-prescribe the 1x kind, and they gave me a yeast infection! This just goes to show that the vaginal microbiome is always changing, as is what the body needs.)

By February, I was opening capsules of the probiotic Femdophilus to mix into solid coconut oil and insert as a makeshift vaginal suppository for when the itching got bad, which is typically associated with yeast but I always attributed to dysbiosis. It was a wild approach, thinking about it now, but it was a tip from my ND and it worked when I needed it to.

Healing from Vaginal Dysbiosis

By late spring, when that ND had helped to stabilize me but didn’t know how to fully resolve my symptoms, she referred me to another ND, whom I saw four times between May and September. (To anyone who has been motivated enough to pay out of pocket for the help of a specialist who doesn’t have to contract with provider networks because their knowledge is so sought after, my heart goes out to you.)

What Is the Mycobiome?

In our first 15 minutes together, this specialist identified an important factor in what was causing my symptoms, one about which I think her instinct was right: something fungal was going on. After taking the number of courses of antibiotics I had, she said, there had to be.

While infinitely smaller than the bacteriome (so much so that it is sometimes called the “rare biosphere”), the mycobiome interacts with it closely. The vaginal microbiome cannot be comprehensively studied without considering the role of the vaginal mycobiome or hormone health!

While the vaginal mycobiome has not been fully characterized, meaning some of the sequences haven’t been identified, we do know that it contains at least 11–20 different genera, most of which are Candida. Candida lives in the gut as well as in the vagina (you have a gut mycobiome too), and research shows that a decrease in anaerobic bacteria or a shift in your Firmicutes to Bacteriodetes ratio (too far in either direction can lead to issues) can promote Candida overgrowth. As with many kinds of bacteria, Candida, among other fungi, is not inherently bad — you want some of it — but too much can be.

Can the Mycobiome Cause Vaginal Infections?

After giving my kidneys and adrenals some love and using nutrients and herbs to promote healthy microbial balance in my gut, the fact that I was still experiencing some UTI and vaginal symptoms led the ND to take a more aggressive approach. She prescribed fluconazole, 200mg every three days.

In mid-September, I took the first seven of 15 capsules before pausing, when my gynecologist advised that taking that much fluconazole could pose a danger to your liver enzymes; when I raised my concern with the ND, she said once every three days wasn’t dangerous. I don’t know who was right. I will say that, not long after taking seven more of the fluconazole (I saved one), I did begin to experience GI symptoms that continued to worsen for two months until I started taking Seed’s DS-01® Daily Synbiotic (a synbiotic is a combination probiotic and prebiotic). My theory, which research supports, is that the fluconazole wiped out my intestinal Candida (I have the GI Map results to prove it), causing dysbiosis there.

After taking the fluconazole, though, something else happened that was magical. For the first time in two years, I finally started to feel better. For one perfect early October weekend, nothing was vaginally wrong with me.

Of course, pharmacies stopped stocking the generic of Nuvaring that I liked, so I had to switch to the other generic, which I knew my body didn’t like as much and it put up a fight about when I switched back. It took three months for my cycle to normalize, even though the rings contain the same hormones in the same amounts and are made of the same materials. (The ND told me there are differences between manufacturers, but I scoured the packaging of one, searched the manufacturer website of the other, and cannot for the life of me figure out what my body was reacting to.)

Over the past several months, I’ve had odor on occasion maybe twice for one day, and not at all recently. I can have sex without noticing odor afterwards, or worse, during. My pH is consistently normal (you can order test strips) and my gynecologist consistently says my estrogen levels look normal or a little low but okay (a gynecologist can tell this from an examination). I’m not itching in the middle of the workday, waiting for that unknown vaginal infection to turn into a UTI too. (Once, I am almost certain that either I had a Candida UTI or my treatment with many, many doses of herbs suppressed bacteria so much that it gave way to a yeast infection — who knows?)

I think there was truth to the ND’s instinct, and yet she never described specifically what fungi might have been contributing to my symptoms. While I am not a scientist, all of those close reading papers I wrote at university taught me to make connections among disparate topics, and as I am someone who lights up when going down scientific rabbit holes, I often emerge with ideas for research directions. Research on the role of the vaginal mycobiome in microbiome eubiosis is one of them.

How the Microbiome Influences Your Immune System, Nervous System, and Vaginal Health

You — as your collection of 38,000,000,000,000 (38 trillion) microbes — will never be the same as you are in this moment. It’s a fun thought to bring you into the present whenever you need to feel grounded, or when you need a reminder of all that your body (microbes included) does for you.

Knowledge about the human microbiome (this phrase actually refers to a collection of microbiomes in the body) has skyrocketed in recent years. Microbiome research began to take off only two decades ago, thanks to sequencing technologies that emerged from the Human Genome Project, with $1.7 billion spent on research since 2009.

What’s so cool about the world of the micro is that invisibly, it influences your physical, emotional, and mental experience of life. The more we understand it, the greater our ability to change our mood and behavior and to prevent and solve our health problems, on an individual and collective scale.

Only 7% of your microbiome can be explained by inheritance — the rest is shaped by how you live. Our microbiome develops rapidly during the first three years of life, but the factors that shape it during that time, including nutrition, environment (including who we live with!), and antibiotics and antimicrobials, continue to do so at every stage of life.

It may be true that bacteria influence what we look like and how we feel, but it’s also true that we have agency to determine our health journey throughout life.

What Is the Microbiome?

A microbiome is a collection of microorganisms in a specific environment. It includes not only the microorganisms themselves but also their genes, structural elements, metabolites, and surroundings — collectively forming a unique ecosystem. (To allow your inner nerdiness to light you up, as mine often does, read Seed’s Microbiome 101 or tap through Seed University’s stories.)

Technically, a microbiome includes not only bacteria but also fungi (also referred to as the “mycobiome”), viruses (the “virome”), and many other microorganisms. The term “microbiota” refers to just the bacteria themselves.

As you may have guessed, multiple microbiomes exist harmoniously within the body. The gut microbiome is the most well-known, but there are also vaginal, oral, and skin microbiomes. Even your eyes, lungs, and urogenital tract have microbiomes.

The natural world has microbiomes, too, composing a whole other body of research and development that I encourage you to read about but that we won’t cover here.

The Roots of the Microbiome

Scientists, integrative and naturopathic clinicians, and nutritionists are increasingly noting the fact that health starts in the gut.

Fiber 101

In the gut, microbes create short-chain fatty acids and other metabolites when they break down fiber. Fiber is found in all plants, although is present in higher quantities in some plants than in others. Microbes act on soluble fiber (as opposed to insoluble fiber) to produce metabolites.

Viscous fibers allow bacteria to produce metabolites known as short-chain fatty acids. There are many types of short-chain fatty acids, the most abundant of which are:

· Acetate

· Propionate

· Butyrate

Butyrate in particular receives a lot of attention because the body can’t make it on its own — it derives it largely from microbial biochemical reactions — and it’s important! Among its many benefits, it helps to:

· Give energy to the cells composing the gut lining

· Reduce oxidative stress and prevent inflammation by stimulating production of glutathione, your body’s most important antioxidant for detoxification

· Manage the production of regulatory T-cells to defend against pathogens and certain autoimmune conditions, including those involving inflammation of the central nervous system

· Support metabolic health by regulating blood sugar and stimulating production of hormones

Different gut bacteria produce different SCFAs. Interestingly, herbal medicines may also produce SCFAs by modulating the gut microbiota. Berberine, for example, contributes to the production of acetic acid and propionic acid.

Fermentable fibers feed your gut bacteria (they’re also known as prebiotics), positively changing the gut microbiome. They do this by increasing quantities of the protective gut bacteria Bifidobacterium, for example, and by improving your Firmicutes to Bacteroidetes ratio.

Together, these two phyla compose 90% of the gut microbiome. Having more Firmicutes like Lactobacillus is associated with a healthier gut and leaner body type (they also produce butyrate).

3 Roles of the Microbiome

Balanced flora in the gut support balance in the body by interacting with your immune system, brain, and hormones.

The Gut-Immune Axis

You might have heard that you receive your first microbes from your biological mom when you’re born, a process called seeding.

Metabolites produced by maternal microbes, immune cells, and antibodies create the prenatal immune system, allowing newborns to mount an immune response directly after birth, and a baby’s immune system continues to develop throughout the first 2-3 years of life alongside their microbiome. This is one reason it’s so important to protect baby’s microbiome by preventing antibiotic overuse, which can compromise the microbiome and thus immunity.

From our first breaths (and possibly even before we’re born), the relationship between our microbiome and immune system is clear, and there’s even a name for it: the gut-immune axis.

Gut microbes communicate with immune receptors and cells by producing those metabolites noted above. They also maintain proper immune response by:

· Controlling inflammation

· Inducing the release of cytokines and chemokines, which move throughout the circulatory system and lymphatic system (a part of your immune system)

· Reinforcing gut barrier integrity by supporting the presence of tight junctions, intracellular connectors lining your gut (intestinal hyperpermeability can provoke autoimmunity and cause many other symptoms)

· Nudging out pathogens by competing for nutrients and space and producing antimicrobial substances

The Gut-Brain Axis

As someone who used to write for neuroscientists, I may be biased in saying that the gut-brain axis may be a more popularly recognized phrase than the gut-immune axis. All the same, this network of physiological pathways connecting the gut and brain is implicated in many psychological, psychiatric, and neurological disorders, including Alzheimer’s, Parkinson’s, autism, schizophrenia, depression, anxiety, multiple sclerosis, and irritable bowel syndrome (which has recently been recognized as a miscommunication between your brain and gut cells).

Neural, endocrine, and immune communication with the central nervous system is bidirectional and influenced directly by the gut microbiome. Your gut microflora stimulate the release of hormones from what are known as enteroendocrine cells, specialized endocrine cells in the gut (the enteric nervous system is the nervous system in your gut). Enteroendocrine cells also produce neurotransmitters such as serotonin, which makes you feel calm and happy, that can travel to the brain or act on nearby enteric neurons.

The Vagus Nerve

The primary way in which bidirectional communication takes place, however, is via the vagus nerve, which has received a lot of attention within the wellness space for its role in calming the nervous system. (For a primer on polyvagal theory and the twelve cranial nerves, of which the vagus nerve is the tenth, plus exercises to quickly reset your nervous system, read Accessing the Healing Power of the Vagus Nerve by Stanley Rosenberg.)

The vagus nerve comprises both afferent (going to the brain) and efferent (coming from the brain) neurons. In Your Body Is Your Brain, Amanda Blake describes somatic intelligence, or how afferent nerves inform your brain about sensation, suggesting that your brain may not be the know-it-all it thinks it is: “A small group of cells in the amygdala—a tiny bit of brain involved in assessing danger—fires six to eight milliseconds after each heartbeat. The implication: when there’s something to be scared of, your rapidly beating heart lets your brain know.”

Afferent nerves respond to stimuli including nutrients, peptides, hormones, and cytokines, so microbiota can affect signaling to the brain by inducing the release of these factors from enteroendocrine or gastrointestinal immune cells.

By affecting vagus nerve signaling, microbiota may change vagal tone, or the dominance of your parasympathetic nervous system in the dynamic interaction between the parasympathetic (rest and digest) and sympathetic (fight or flight) branches of the autonomic nervous system.

Another topic that’s talked about in the health and wellness community is heart rate variability (HRV). As it turns out, HRV is also a measure of parasympathetic activation, as cardiac vagal tone.

The Gut-Vagina Axis

Over the past two years, my health journey has mostly involved my vaginal microbiome. I wrote about my experience with frequent UTIs and ureaplasma. At the same time as all of that was happening, and for a period of a little over a year after the ureaplasma resolved, I was having vaginal problems too.

They were heart-wrenching and devastating and reduced me to tears, repeatedly. They made me more resilient, taught me how to listen to my body and manage stress when I sense that something is off, and launched my intellectual journey into microbiome sciences.

Considering that the gut microbiome has systemic, whole-body effects, is it possible that connections also exist across microbiomes? For example, could the gut microbiome and vaginal microbiome be linked?

The Estrobolome and Estrogen Metabolism

It’s a fairly new discovery that your gut microbiome changes your hormones. A unique microbiome within your gut microbiome, known as the estrobolome, has special genes that allow these bacteria to metabolize estrogen, a hormone that carries out many important functions in the body.

Once estrogens circulating in the bloodstream have done their job, they wind up in the liver, where the majority of estrogen metabolism takes place. Some estrogens are reabsorbed, while others are destined for removal. Those that travel to the gut are further metabolized by the estrobolome in a process called deconjugation.

Healthy gut function supports hormone balance, and in return, healthy estrogen levels support healthy gut function by maintaining gut barrier integrity; however, you need the right balance of microorganisms in your gut to support healthy estrogen levels.

Some studies have found that an imbalance in certain populations of gut bacteria (which could be caused by taking antibiotics, for example) disrupts the deconjugation process (and decreases urinary estrogens, which suggests a direction for research on the urogenital microbiome).

Figure from Cell Host & Microbe.

Hormone Balance and Vaginal Health

In the vagina, estrogen facilitates the growth of lactobacilli — which has a protective effect — by instructing your epithelial cells to produce glycogen, which existing lactobacilli metabolize into lactic acid (CH₃CHCOOH). This reaction creates an acidic environment in the vagina, with pH levels between 3.5 and 4.5, further promoting growth of lactobacilli and inhibiting growth of disruptive bacteria. (Two enantiomers of lactic acid exist, D-lactic acid and L-lactic acid, with D-lactic acid exhibiting more protective effects than L-lactic acid, but both kinds exhibit positive effects.)

In addition, a healthy vagina dominated by Lactobacillus species naturally maintains the integrity of the vaginal epithelial barrier, a physical and immunological barrier. The lactobacilli produce certain proteins and antibodies that prevent pathogens from contacting vaginal epithelial cells and neutralize any antigenic microbial products that look like a threat. Lactic acid also upregulates expression of tight junction proteins in vaginal epithelial cells — your vaginal microbes support the presence of tight junctions, just like in the gut!

The gut microbiome may serve as a reservoir for pathogens that can disrupt your vaginal microbiome, so maintaining the vaginal epithelial barrier is important. Interestingly, the naturopathic doctor I was working with for the UTIs noted on one occasion that we had to “find the reservoir.”

My Inner World

While I wouldn’t wish to repeat the experiences that prompted me to learn about the vaginal microbiome, those experiences and my research have led me to develop a deep respect for the innumerable ways in which the body is intricately connected. They’ve led me to see the world within the human body as one in which chemical messengers can be catalogued and known, with still so much to discover — and a whole other world of biodiversity waiting to be known outside.

This perspective shift feels like a spacious cognizance of all of the ways in which microorganisms are always communicating with the immune system, the brain, the vagina at once, working cohesively to allow us to make love, manage stress, fight infection, and carry out our beautiful lives.

Mitochondria: The Secret to Having Energy and Aging Gracefully

On New Year’s Day, a crowd gathered on the shore of the Puget Sound, anticipatory energy in the air. The sun was shining on my skin, warming my body in preparation for the 47-degree temperatures (both in the water and in the air), and everyone was stripping down to their swimsuits.

This New Year’s tradition, lovingly referred to as the “Polar Plunge,” is an example of cold therapy, which is thought to have benefits for your mitochondria and immune system as well as for increasing longevity.

In Lifespan: Why We Age — and Why We Don’t Have To, David Sinclair notes cold therapy as one way to expose your body to the right level of stress to slow down the aging process. Sinclair’s book hinges on the premise that just enough stress increases longevity by inducing favorable and protective biological processes, such as maintaining the integrity of mitochondrial DNA.

What Do Mitochondria Do?

Mitochondria regulate cellular energy metabolism by producing adenosine triphosphate (ATP) via oxidation-reduction (a chemical reaction involving an exchange of electrons). The nutrition we put in our bodies provides electrons that are channeled into what’s known as the electron transport chain. Protons are pumped into the intermembrane space (mitochondria have two cell membranes), creating a proton-motive force that provides the energy needed for ATP synthesis via mitochondrial oxidative phosphorylation, only this process isn’t perfectly coupled to ATP synthesis, partly because uncoupling proteins can tell protons to move from the intermembrane space into the mitochondrial matrix. In fact, this is thought to be responsible for 20–30% of our basal metabolic rate!

Why Cold Exposure Works

Uncoupling proteins protect our mitochondria against oxidative damage. Free radicals, also called reactive oxygen species, react easily with other molecules in ways they’re not supposed to, and overproduction of free radicals creates oxidative stress, which leads to DNA damage and throws the body into a state of inflammation.

Cold exposure increases the number of mitochondria in our bodies and activates uncoupling proteins, resulting in improved mitochondrial function and faster metabolism. When we take cold showers, sleep with fewer covers at night, take an ice bath, or run into a near-freezing body of water, we feel good afterwards because our mitochondria are alive and happy.

Another way to experience the benefits of cold is hot/cold therapy, which stimulates blood flow and moves oxygen through our bodies. Warm water moves blood to our limbs, while cold water causes our blood vessels to constrict and direct blood flow to our hearts, to stay warm.

To try this the next time you take a shower, alternate showering in warm water for 3 minutes and then turning the water as cold as you can stand for 30 seconds. Some hot springs also have cold pools, so you can alternate between warm and icy cold temperatures.

Other Ways to Care for Your Mitochondria

Remember when I said that cold increases the number of mitochondria you have? This mitochondrial biogenesis is stimulated by AMPK (AMP-activated kinase) pathway, which senses how much ATP is in your cells and can actually reprogram your metabolism and support metabolic balance at the whole-body level. Why would your mitochondria reprogram your metabolism? The answer has to do with glucose.

Glucose Balance

Glucose is a simple sugar, the kind our bodies use to create energy in the form of ATP. As Jessie Inchauspé describes in Glucose Revolution: The Life-Changing Power of Balancing Your Blood Sugar, in plants, glucose can be stored as starch (long chains, mostly found in root vegetables), fiber (linked chains, which makes them indigestible, found in all plants and especially in trunks, branches, and leaves, if we’re talking plant anatomy), fructose (found in fruit), or sucrose (glucose + fructose, smaller than lining up the two molecules side by side, which helps plants to store energy).

There are many kinds of carbohydrates, and other macronutrients can be turned into glucose as well (metabolic flexibility is a measure of how well your body is able to burn fat instead of glucose and is an indicator of healthy metabolism). Regulating your blood glucose levels is important because glucose spikes deliver more glucose to our cells than they need. According to the Allostatic Load Model, when this happens, mitochondria can’t process all of that glucose at once, and free radicals are released, damaging our mitochondrial DNA and leading to oxidative stress. Then, because our damaged mitochondria can’t convert glucose to energy efficiently, our cells starve, and we feel tired.

To flatten your glucose curves, Jessie outlines 10 “hacks," which I'll list and then explain in my own words:

1. Eat Foods in the Right Order

This trick works because of the plant anatomy we talked about above. Eat vegetables (fiber) first, protein and fats second, and grains and other starches last. The fiber reduces the action of alpha-amylase, an enzyme that breaks down starch into glucose; slows the digestion process, balancing our blood sugar; and makes it harder for our small intestine to absorb glucose. Absorbing less glucose doesn’t make us tired; in fact, the opposite is true — if we’re following no.1, we have sustained energy throughout the day and increased metabolic flexibility.

2. Add a Green Starter to All Your Meals

Starting with a salad is a simple way to remember to eat fiber first. It’s an opportunity to be creative, too — almost any vegetable(s) will do!

3. Stop Counting Calories A glucose-flattening diet allows you to eat more calories and lose more weight than you’d be able to with more dramatic glucose curves.

4. Flatten Your Breakfast Curve

Given that breakfast is the first thing you put in your body in a day, there is more potential for a spike! Be kind to your body by swapping sweet for savory breakfasts to dramatically reduce the spike.

5. Have Any Type of Sugar You Like—They’re All the Same

Even better, opt for sweet spices like cinnamon, 100% chocolate (cacao nibs or bars), berries, and other sweet-tasting foods that are low in sugar.

6. Pick Dessert over a Sweet Snack

The reason for this is the same as in no.1, in addition to the fact that snacking increases the time our bodies spend in a post-prandial state. The time our bodies are not in a post-prandial state is when they’re able to replace damaged cells with new ones and our insulin levels come down.

7. Reach for Vinegar Before You Eat Any kind of vinegar has been shown to reduce the effect of what you put in your body after. Mixing a simple vinaigrette of olive or avocado oil and white or apple cider vinegar is a simple way to add vinegar and a green starter at the same time.

8. After You Eat, Move When you spend even 10 minutes walking after a meal, you tell your mitochondria to turn those nutrients into glucose to move your muscles, which moves glucose our of our bloodstream. If you’re going to work out, the time to do so for the greatest reduction to glucose and insulin spikes is after a meal, but before a meal works great too. Fasted exercise (i.e., first thing in the morning) creates free radicals, but because exercise improves the body’s ability to fight free radicals, the net effect is positive.

9. If You Have to Snack, Go Savory

A glucose spike is accompanied by a spike in insulin. Insulin’s role is to remove blood glucose. It does this by storing glucose as glycogen (in our liver and muscles) or as fat. Fructose can only be stored as fat because it can’t be turned into glycogen. So, the same number of calories as a sweet food (containing fructose or sucrose) is more likely to lead to weight gain than as a savory food. Fructose also increases glycation, in which glucose molecules attach to other molecules, further contributing to oxidative stress, inflammation, and aging. In fact, David Sinclair notes that we become more insulin-resistant as we age due to a process called ex-differentiation, in which our cells lose their identity due to DNA damage. We also lose glucose transporters.

10. Put Some Clothes on Your Carbs Adding protein, fiber, and/or fat decreases the amount of insulin released in response and keeps us feeling full for longer. Ghrelin, the hormone responsible for hunger, bottoms out quickly and then just as quickly rises even higher when we eat a carb on its own. Proteins take longer to make us feel satiated but keep us feeling full the longest. Fats fall somewhere in between.

Hormones Are the Stars

It's worth noting that many hormones play a role in glucose homeostasis, including how our body derives and stores energy. When glucose is no longer freely circulating in our bloodstream, our bodies have two choices: glycogenolysis (turning stored glycogen into glucose, promoted by glucagon; in contrast to glycogenesis, the synthesis of glycogen from glucose, promoted by insulin) or gluconeogenesis (creating glucose from non-carbohydrate sources). Insulin and its opposite, glucagon, regulate these processes.

Other hormones involved in glucose homeostasis include cortisol, epinephrine, amylin, and GLP-1, or glucagon-like peptides, and all of these hormones are produced in different places in the body! For example, ghrelin is made in the stomach; amylin, which slows stomach emptying and inhibits the release of glucagon, is made in the pancreas; and GLP-1, which stimulates insulin secretion and slows stomach emptying, is made in the small intestine.

High-Intensity Interval Training

Vigorous exercise requires a lot of glucose and therefore activates the AMPK pathway. It also activates hypoxia-inducible factors as in the HIF-1α pathway. In the same way that the AMPK pathway senses the level of ATP in a cell, the HIF-1α pathway senses how much oxygen is in a cell. When the cell in a state of hypoxia, or lack of oxygen, mitochondrial respiration (the process by which mitochondria produce ATP) can’t happen, and biogenesis is inhibited through altered gene expression.

A little mitochondrial stress, however, is good: when there is slight hypoxia, as in vigorous exercise, your body manufactures more mitochondria, giving you more energy, and stimulates the formation of blood vessels, to transport oxygen throughout your body. This is one reason that the more you exercise, the less easily fatigued you are.

Naturopathic Approaches

One of the first areas a naturopathic doctor worked on with me when I came to her was energy-stabilizing support. One aspect of naturopathic medicine that I find fascinating from a biochemistry perspective is its focus on giving your body the micronutrients and cofactors the body needs to carry out the natural processes that make us feel good.

I took a supplement called Pure Endurance (Physician’s Standard), which facilitates oxygen and nutrient transfer to cells and muscles (by now, the importance of these processes should make sense!). Specifically, it contained Vitamins B1 and B2, selenium, acetyl L-carnitine, L-carnosine, CoQ10, and lithium.

B-vitamins serve as cofactors or coenzymes required for energy metabolism, and Vitamins B1 and B2 are involved in the tricarboxylic acid cycle. Selenium has a reputation for improving thyroid function, but it also improves mitochondrial function (the thyroid affects mitochondrial biogenesis).

Many more ingredients can improve mitochondrial dysfunction, among them L-carnitine, a transporter in mitochondrial metabolism, and CoQ10, a cofactor in the electron transport chain. Carnosine may prevent glycation. Lithium may increase mitochondrial respiration and prevent the shortening of telomeres, which happens as we age.