Menopause's Inflammatory Impact and How to Reduce It
If you’ve read the articles in our menopause series so far, you know that a lot of the issues that pop up during and after menopause are due to decreased levels of hormones, such as estrogen and progesterone throughout the body.
Additionally, other hormones, like DHEA and pregnenolone, drop naturally with age, and consequently, during menopause as well. These hormones are often referred to as “precursors” to other hormones like estrogen. Lack of DHEA and pregnenolone can contribute to decreased levels of estrogen and progesterone as well.
So what is it that these hormones actually do to protect the body, and how does losing large amounts of them hurt the body and increase inflammation? We’ll discuss some of the issues this inflammation causes, including deteriorating bone health, joint health, muscle health, and brain health.
Bone Health
Bone health is something women need to be very careful about in the perimenopausal, menopausal, and postemenopausal stages. To understand why, we need to know about osteoclasts and bone resorption. Osteoclasts help to heal and grow bones by breaking down the bone tissue and releasing the minerals into the blood. This is a process called resorption. While this process is very important in maintaining blood calcium levels, there can be too much of a good thing. When left unchecked, excessive bone breakdown by osteoclasts can lead to fragile bones (1).
When the body is in an inflamed state, T cells will recruit and prolong the life of osteoclasts via interleukin-6 (IL-6). If osteoclasts are left to break down bones more than they should, we run into bone health issues. However, when we have adequate amounts of estrogen, the estrogen is able to inhibit IL-6, preventing excessive bone breakdown from occurring. Additionally, decreased estrogen can sensitize the bones to the effects of parathyroid hormone (PTH), which will also increase effects of bone resorption (2).
What happens when bone health is compromised in these menopausal stages due to a lack of estrogen? Women can begin to lose bone density leading to osteopenia or even osteoporosis down the road.
Regarding precursors to estrogen, research has found that DHEA may actually preserve bone mass (as well as muscle mass) in older women (3). Pregnenolone also can prevent osteoporosis and bone destruction (4).
Joint Health
We are learning that estrogen and other hormones can also serve protective effects on joint cartilage. Researchers have found connections between decreased estrogen and arthritis, including osteoarthritis, which is a degenerative joint disease. In animal studies, researchers have found that estrogen protects joint integrity through complex molecular mechanisms. For example, estrogen can inhibit cyclooxygenase-2 (COX-2) mRNA expression in bovine joint cartilage cells. COX-2 is an enzyme that produces inflammatory prostaglandins. Estrogen prevents these inflammatory effects and protects joint cartilage cells from damage from reactive oxygen species (5).
Muscle Health
Concerning muscle mass, estrogen (and its precursor hormones) once again have an effect. Estrogen is helpful for both muscle mass and strength, and in postmenopausal women, research has found a rapid decline in muscle mass. While there is no significant difference in middle-aged men and women’s muscle responses to nutrition and training, when research looks at postmenopausal women, they have a reduced muscle response to nutrition and training when compared to men of the same age (6).
Without the protective effects of important hormones, menopausal and postmenopausal women are opened up to arthritis, joint pain, stiffness, muscle aches, and pains.
Brain Health
As you may remember, estrogen also plays a role in brain health and keeping neuroinflammation down. In chronic neuroinflammation, microglia cells are continually activated to produce inflammatory cytokines and remove damaged neurons. If this is a continuous state of the brain and central nervous system, this opens a person up to several neurodegenerative diseases, including multiple sclerosis, Alzheimer’s, and Parkinson’s disease. Estrogen has inhibitory effects on neuroinflammation and specifically, on microglia cells, which protects the brain against these degenerative diseases. It also protects against more minor conditions like brain fog, which is also affected by microglia cells (7).
Pregnenolone is a steroid hormone that is produced by the brain and considered a neurosteroid. It regulates mood and memory and serves neuroprotective, neuroplastic, and neurogenesis roles. Lack of pregnenolone is associated with depression and impaired memory as well as fluctuations in hormones, such as estrogen. As pregnenolone decreases naturally with age, this is something we want to watch (8).
DHEA has similar effects on the brain, and lack thereof has been associated with cognitive decline, such as Alzheimer’s and dementia (9).
Women lose much of their neuroprotection when precursors to estrogen (like pregnenolone and DHEA) and estrogen levels decrease.
Weight Gain
If you remember from our first menopause article, menopause has an effect on weight gain as well. Before menopause, women with balanced hormones tend to gain weight in their buttocks and thighs. After menopause, the hormone shifts cause women to gain weight in the abdominal area in the form of visceral fat, which is very inflammatory. Abdominal adiposity (obesity) often increases in post-menopausal women, and this can cause increased levels of adipocytokines (cytokines secreted by fat tissue). These include c-reactive protein (CRP), IL-6, and tumor necrosis factor α (TNFα). These are all very inflammatory for the body. This inflammation can also lead to issues such as type 2 diabetes, which then makes post-menopausal women more at risk for conditions like Alzheimer’s (10, 11).
Importance of Anti-Inflammatory Lifestyle and Supplements
When women lose the anti-inflammatory effects of hormones during menopause, it’s important to think about how they can decrease inflammation in other ways. Lifestyle factors absolutely play a role, including getting sufficient sleep, lowering stress levels, eating a nutritious and anti-inflammatory diet, and controlling toxin exposure. Along with these factors, there are some key supplements to help keep inflammation down.
Vitamin D
Vitamin D is a fat-soluble vitamin and hormone. It’s found in cod liver oil, tuna fish, salmon, and swordfish. It’s also found in egg yolks and beef in small amounts. Our bodies can convert sunlight into vitamin D, though some struggle with this process, and the body’s ability to do this conversion decreases with age.
It’s really important to have your vitamin D levels checked, and most people will need to supplement with it, especially menopausal and postmenopausal women. It can help with calcium absorption as well as bone growth and remodeling to help these women with bone health. It also reduces overall inflammation, helps with immune function, helps with neuromuscular function, and cell growth.
Functional medicine practitioners like to see vitamin D levels in what is called a “functional range.” Functional ranges are often smaller ranges than lab ranges. A functional range is determined by what is considered optimal for body function. This optimal range is often in the upper limit of the lab range for nutrients.
Lab range for vitamin D is 30 - 100 ng/mL. In our office, we like to see vitamin D levels around 85-88 ng/mL. If they are lower than this, we will dose vitamin D accordingly.
Vitamin D is a fat-soluble vitamin, so it can reach toxic levels if you take too much.
Doses of 40,000 - 100,000 IU of vitamin D can create toxic levels in the blood. At blood levels of > 150 ng/mL individuals can experience symptoms of vitamin D toxicity. The dose for each person varies based on the body’s needs.
In winter, it is especially important to take vitamin D due to lack of sunlight. If you are taking vitamin D, we recommend working with someone that does functional medicine to get your levels tested and find the right dose for you. We measure all of our new patients’ blood levels for vitamin D since most people are deficient. We will then do follow-up labs to check vitamin D levels and adjust the dose accordingly.
Here is an example of a vitamin D lab below:
You can see that prior to treatment, this person had a vitamin D level of 28.6, which is below lab range. The follow up lab was drawn after the patient was taking 10,000 IU of vitamin D for a few months.
Boron
Boron is an element you might remember on the periodic table. It is found in leafy vegetables, such as spinach and kale. It is also found in raisins, nuts, prunes, non-citrus fruits, coffee, dried beans, and potatoes. Like vitamin D, boron also plays a role in bone health by preventing calcium loss as well as bone demineralization from the body. Boron supplementation has repeatedly been shown to markedly reduce urinary excretion of both calcium and magnesium and to increase serum levels of estradiol and calcium absorption in peri- and postmenopausal women. Additionally, it helps your body use important vitamins and minerals, and it plays a role in brain health.
Boron also extends the half-life of vitamin D and of estrogen. The half-life of a substance is the time it takes for the substance to break down to half of its original amount. Therefore, boron allows vitamin D and estrogen to last longer in the body. Vitamin D and boron are great to take together!
There is no set daily intake amount for boron. However, there is an upper limit of 20 mg/day for individuals 18 years and older. In research, none of boron’s benefits appear at doses less than 3 mg/day. Therefore, we typically recommend dosing at least 3 mg per day.
It should be noted that boron also helps to increase sex hormone levels in both males and females. In females, boron has been found to increase estradiol and testosterone levels (which are often low in menopausal and post-menopausal females). In males, it has been found to significantly increase free testosterone levels, decrease estrogen levels as well as decrease inflammation markers CRP (50% decrease) and TNF-α (30% decrease). This was all seen after ONE week of taking 6 mg of boron daily (12). That ‘s pretty remarkable!
Omega 3-fatty acids
Omega 3-fatty acids are polyunsaturated fatty acids that your body cannot make on its own. Therefore, you have to get them from your diet. The three most important types are ALA (alpha-linoleic acid), DHA (docosahexaenoic acid), and EPA (eicosapentaenoic acid).
ALA is found in flax seeds (freshly ground), flaxseed oil, chia seeds, walnuts, and hemp seeds. DHA is found in fatty fish and fish oil. It can also be found in meat, eggs, and dairy from grass-fed animals. EPA is found in animal products, such as fatty fish and fish oil. It is also found in some microalgae.
Omega 3s are extremely important for brain health and for inflammatory conditions. They are able to lower the effects of inflammatory factors in the body, such as CRP, IL-6 (remember the effects of IL-6 on bone health?), and tumor necrosis factor.
To get a handle on what dosing is needed, we will often run an omega panel to look at the individual’s omega levels.
This particular patient had a neuro-inflammatory condition, so we were dosing with a lot of DHA to help bring down brain inflammation. You can see that it became a little high. With an omega check, we were able to lower the dose of DHA that the patient was taking and tweak a couple of other things to take full advantage of the anti-inflammatory benefits of DHA.
NOTE: If you find yourself burping up fish oils or other fats. You likely have an issue with your gallbladder. If you add this and still find yourself burping up your fish oil. Stop the fish oil for 2-3 months and work on gallbladder function. We often use Bilemin from Apex Energetics to help with fat digestion. One capsule 3 times daily for 2-3 months. If you do NOT have a gallbladder, we recommend continuing this product indefinitely.
Turmeric/Curcumin
Turmeric is a spice that is often found in Asian cooking. It is what gives curry its yellow color. It also contains various medicinal compounds, the most important being curcumin.
Curcumin is an extremely powerful anti-inflammatory. It has antioxidant effects, can prevent and potentially treat cancer, and it improves brain function. It can prevent and treat neuro conditions such as depression and Alzheimer’s. There is also evidence that curcumin can prevent and treat type 2 diabetes, which is a concern in menopause (13).
Resveratrol
Resveratrol is a part of a group of plant compounds known as polyphenols, which act as antioxidants. You can find resveratrol in the skins and seeds of red grapes, and skins and seeds of berries. It is most concentrated in Japanese knotweed.
Resveratrol acts as a strong antioxidant as well as a strong anti-inflammatory. Resveratrol can reduce pain in postmenopausal women (14). It has also been shown to improve mood and cognition (15).
We like to use the active form of resveratrol (trans-resveratrol) from Japanese Knotweed in a liposomal formulation. This allows enhanced absorption.
Glutathione
Glutathione, the superhero, has over 150,000 research articles on Pubmed with most of the research being done within the past 10 years. Glutathione is often referred to as the “Master Antioxidant” or the “Mother of Antioxidants.”
Glutathione is an essential antioxidant that is found in all human cells and tissues. It is needed to activate other well known antioxidants like vitamin C and E. As an antioxidant, it is able to protect cells from the damage of oxidation. Without it, cells will perform poorly or die, driving oxidative stress which has been found to drive degenerative conditions (16).
It is important to supplement with glutathione as its production often decreases with age.
Glutathione levels can also be affected by stress, environmental toxins, and poor diet. Glutathione is able to lower oxidative stress, therefore lowering inflammation. It may assist in preventing osteoporosis and cognitive issues. Our office, as well as other functional medicine clinics, find that patients dealing with a chronic health issue, no matter what age, are depleted of glutathione.
We like to use glutathione precursors as well as bioactive and reduced glutathione in a liposomal preparation.
Here is an example of glutathione levels before and after supplementation:
Glutathione dosing should be based on the individual’s glutathione blood levels as it is possible to take too much glutathione. There are many things that can affect how much glutathione your body needs. Therefore, we recommend working with a functional medicine practitioner to help you find the dose that is right for you.
It’s important to note that many of these important anti-inflammatories are more powerful when taken together. For example, boron allows vitamin D to be more effective, and vitamin D can increase the effectiveness of resveratrol. Resveratrol and curcumin are also more effective against inflammatory disorders when they are taken together.
Though menopausal changes can cause your body to become more inflamed, working with a doctor that specializes in functional medicine can make a world of difference. We work with our patients to seek out root health issues and can customize a care plan based on individual needs. Whether you have been post menopausal for many years or are just transitioning into menopause, we can help you feel at your best. For your convenience, we work with patients via telehealth or in person.
Works cited: