Natalie Crawford, M.D.’s
Perimenopause Support
Protocol overview
Last updated: May 13, 2025
9 Nutrients
Folic Acid
400mcg
During perimenopause, fluctuating hormones can place added stress on the body’s repair systems. Folic acid supports healthy cell division, DNA repair, and methylation, key processes that help maintain cardiovascular, neurological, and tissue health through this transitional phase. (For a precise explanation of why folic acid is recommended instead of methylated folate, and additional information relating to the MTHFR gene, please review the Warning section later in the Protocol). [1]
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Log in or sign upVitamin D3
25mcg
Vitamin D supports healthy cell growth, helps regulate immune function and inflammation, and is essential for calcium absorption and bone mineralization. Adequate levels are important during midlife to maintain skeletal strength and support overall metabolic and immune health. [2]
Omega-3 fatty acids
300mg
Omega-3 fatty acids support cellular membrane integrity and reduce inflammation, which is especially important during perimenopause. They may help ease joint discomfort, stabilize mood, and support heart and brain health as hormonal changes impact systemic inflammation and cellular function. [3]
Coenzyme Q10
600mg
CoQ10 is an antioxidant that supports cellular energy production and tissue repair. In women, it may reduce oxidative stress associated with aging, and support heart, skin, and mitochondrial function during key stages of growth and recovery. [4]
Melatonin
3mg
During perimenopause, shifting hormones can affect sleep and mood. Melatonin helps regulate the sleep-wake cycle and circadian rhythm, while also reducing oxidative stress and inflammation—offering support for restful sleep, emotional balance, and overall recovery during hormonal transition. [5]
Vitamin C
1000mg
Vitamin C supports immune health and collagen production, while also reducing oxidative stress. In perimenopause, it may help lower inflammation and improve joint or muscle pain by modulating inflammatory markers and supporting connective tissue integrity. [6]
Vitamin E
536mg
Vitamin E is a fat-soluble antioxidant that protects cells from oxidative stress. During perimenopause, it may help reduce inflammation, support skin and cardiovascular health, and has been studied for its potential to ease hot flashes and hormonal discomfort. [7]

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Warnings
If you are pregnant, breastfeeding, or taking anticoagulants, corticosteroids, hormone therapy, insulin-sensitizing medications, or sedatives, consult your healthcare provider.
Many new prenatal vitamins have entered the market which have methylated folate instead of folic acid. Methylated folate is a downstream metabolite of folic acid. Although some people may have difficulty metabolizing folic acid (associated with a genetic mutation, MTHFR), it is very important to realize that only folic acid has been shown to prevent NTD (neural tube defects). Although methylated folate has been shown to result in sufficient blood folate levels, no study exists proving that methylated folate prevents neural tube defects or compares methylated folate vs folic acid. No study like this will ever exist because when something clearly prevents a bad outcome, like a birth defect, you would never allow a group of pregnant people to be at risk for this outcome when you could prevent it. I recommend you take at least 400 mcg of folic acid, in the form of folic acid. If you love a prenatal that has methylated folate, take an additional folic acid supplement. Methylated folate may help a small group of people who have problems metabolizing folic acid when they are not pregnant, but if you are trying to conceive, I recommend adding folic acid as well.
Lifestyle Improvements
During perimenopause, your body is navigating a wave of hormonal changes—fluctuating estrogen and progesterone can affect everything from mood and metabolism to sleep and cycle regularity. Lifestyle support is not optional; it’s foundational. The more consistent you are with the basics, the more resilient your system becomes through this transition.
Start with nutrition. A diet rich in colorful vegetables, fiber, high quality protein, and healthy fats will help stabilize blood sugar, reduce inflammation, and support hormone balance. Fiber is particularly important. It supports gut health and estrogen metabolism, both critical during perimenopause. Try to limit alcohol, highly processed foods, and excess caffeine. These can disrupt sleep, worsen hot flashes, and increase anxiety.
Movement matters. Regular physical activity can reduce hot flashes, improve sleep, and help maintain muscle and bone strength as estrogen declines. I recommend a mix of resistance training, aerobic exercise, and lower-intensity movement like yoga or walking. Even 30 minutes a day can make a difference.
Sleep can become more elusive in perimenopause, so prioritizing good sleep hygiene is key. Aim for 7–9 hours per night. Keep a consistent bedtime, avoid screens before bed, and try wind-down routines like reading, stretching, or mindfulness. If sleep disturbances persist, talk to your doctor, supporting sleep may also support hormonal rhythm and emotional balance.
Stress is a major disruptor of hormonal health. Cortisol, your primary stress hormone, competes with progesterone and can worsen symptoms like mood swings, fatigue, and insomnia. Incorporating daily stress-relieving practices like journaling, breathwork, or even just saying ‘no’ more often can go a long way. Emotional resilience is just as important as physical.
Track your symptoms and your cycle. Many women experience irregular periods, skipped cycles, or worsening PMS during perimenopause. By tracking these changes, you can better advocate for yourself and recognize when additional support is needed.
Perimenopause is not just a time of loss, it’s a time of recalibration. With the right foundational habits, you can feel strong, supported, and informed about what your body needs.
Disclaimer
These statements have not been evaluated by the Food and Drug Administration. Any products and informational content displayed on this page are not intended to diagnose, treat, cure, or prevent any disease.
While this Protocol has been created by health experts, it is educational in nature and not a substitute for personalized medical advice. Always consult with your healthcare provider before starting any new supplement regimen, especially if you have underlying health conditions or take medications.
- Duthie, S. J., Narayanan, S., Brand, G. M., Pirie, L., & Grant, G. (2002). Impact of folate deficiency on DNA stability. The Journal of Nutrition, 132(8), 2444S–2449S. https://doi.org/10.1093/jn/132.8.2444S
- Holick, M. F. (2007). Vitamin D deficiency. The New England Journal of Medicine, 357(3), 266–281. https://doi.org/10.1056/NEJMra070553
- Kiecolt-Glaser, J. K., Belury, M. A., Andridge, R., Malarkey, W. B., Hwang, B. S., & Glaser, R. (2012). Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: A randomized controlled trial. Brain, Behavior, and Immunity, 26(6), 988–995. https://doi.org/10.1016/j.bbi.2012.05.011
- Sangsefidi, Z. S., Yaghoubi, F., Hajiahmadi, S., & Hosseinzadeh, M. (2020). The effect of coenzyme Q10 supplementation on oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials. Food Science & Nutrition, 8(4), 1766–1776. https://doi.org/10.1002/fsn3.1492
- Gholami, F., Mohammadbeigi, S., Rahimi, N., Shafiee, N., Saeedi, L., & Moosazadeh, K. (2022). Effect of melatonin supplementation on sleep quality: A systematic review and meta-analysis of randomized controlled trials. Journal of Neurology, 269(1), 205–216. https://doi.org/10.1007/s00415-020-10381-w
- Block, G., Jensen, C. D., Dalvi, T. B., Norkus, E. P., Hudes, M., Crawford, P. B., Holland, N., Fung, E. B., Schumacher, L., & Harmatz, P. (2009). Vitamin C treatment reduces elevated C-reactive protein. Free Radical Biology and Medicine, 46(1), 70–77. https://doi.org/10.1016/j.freeradbiomed.2008.09.030
- Ziaei, S., Zakeri, M., & Kazemnejad, A. (2007). A randomised controlled trial of vitamin E in the treatment of hot flashes in menopausal women. Gynecologic and Obstetric Investigation, 64(4), 204–207. https://doi.org/10.1159/000101753
- Thakker D, Raval A, Patel I, Walia R. N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Obstet Gynecol Int. (2015) 2015:817849. 10.1155/2015/817849
- Scheffers, C. S., Armstrong, S., Cantineau, A. E., Farquhar, C., & Jordan, V. (2015). Dehydroepiandrosterone for women in the peri- or postmenopausal phase. Cochrane Database of Systematic Reviews, 2015(1), CD011066. https://doi.org/10.1002/14651858.CD011066.pub2