Outline
PGC link to oxidative stress and accelerated aging
Melatonin mechanism of action
How common is pineal gland calcification (PCG)?
Calcification begins in childhood. It is exceedingly rare in young children and was not observed in CT scans in children under 3[1]. About 2-5% of children aged 0–9 have PGC, 32% of youth aged 10–19 have PCG, and 53% of young adults aged 20–29 have visible PGC[2].
Rates of pineal calcification were significantly underestimated previously. Data of 12,000 healthy middle-adult subjects from Turkey indicated that intracranial calcifications occurred with an incidence of 71.6%[3]. In Iran the rate is around 71%, in Ethiopia it is roughly 72%, and in the US it is 70%[2]. It appears to occur without significant differences among countries, regions, and races.
Approximately 70% of the aged 30+ adult population has visible pineal calcification, leading many scientists to deem it normal, idiopathic, and physiologic. However, large amounts of calcification disrupt normal melatonin secretion and are associated with aging and neurodegeneration. The tipping point between natural, age-related and pathological, neurodegenerative calcification (also called acervuli or brain dust) is unclear.
What happens when the pineal gland becomes highly calcified?
Calcification reduces pineal release of melatonin, disrupting the feedback loop with the master clock (SCN); it can lead to sleep disturbances, which can cause a host of health problems.
Because calcification decreases pineal secretion of melatonin and is associated with sleep disturbances, oxidative stress, and accelerated aging, its presence in 70% of the middle adult population is concerning if we wish to extend our lifespans. Aging is a normal process, but steps can be taken to slow the rate at which it occurs.
Which disorders are associated with pineal gland calcification?
Calcification of the pineal gland has been associated with numerous neurological deficits, including early onset of Alzheimer’s disease, migraine, movement disorders, age-related macular degeneration, dementia, hallucinations, cognitive disorders, and schizophrenia[1, 4, 5]. Pineal calcification has also been associated with multiple sclerosis (MS), sleep disorders, defective sense of direction, pediatric primary brain tumor, and mammary carcinoma[2]. PCG was an independent risk factor for symptomatic cerebral infarct (stroke) (odds ratio: 1.35) and intracerebral hemorrhage (odds ratio: 2.36). Major calcification was seen in patients who died of renal disease associated with hypertension[2].
How does melatonin protect against diseases of aging?
The pineal gland is the major source of melatonin secretion in the body, and melatonin has been shown to delay progression of multiple cancers and liver disease. Melatonin has oncostatic and antitumor effects against certain cancers, such as melanoma and cervical cancer[6, 7]. Melatonin killed gastric cancer cells by downregulating AKT and upregulating caspases, which induced apoptosis[8]. Additionally, melatonin protects against liver disease by inhibiting oxidation, inflammation, hepatic stellate cell proliferation, and hepatocyte apoptosis[9].
Amazingly, melatonin can protect against environmental insults and epigenetic changes. Melatonin protected against meiotic defects in eggs caused by an herbicide, fenoxaprop-ethyl (FE). Exposure of mouse oocytes to FE disrupted actin filament dynamics, spindle organization, reduced sperm binding capacity, induced oocyte apoptosis, and changed histone methylation patterns. Treatment with melatonin significantly improved oocyte outcomes[10]. Additionally, melatonin attenuated cigarette smoke-induced endothelial cell pyroptosis (inflammatory cell death) in rats by inhibiting oxidative stress[11]. Since melatonin alleviates exposure effects, pineal gland calcification leaves many organ systems vulnerable to oxidative stress.
Melatonin is also a potent neuroprotective antioxidant. It directly inhibited secretion and deposition of beta amyloid protein and suppressed tau hyperphosphorylation in rodent models of Alzheimer's disease. Serum & CSF melatonin were inversely correlated with AD. In AD animal models, melatonin prolonged lifespans, improved cognitive performance, and preserved hippocampal neuron structure. Positive effects of melatonin were also seen in studies on Parkinson's disease, ALS, MS, and Huntington's disease in animal and human models[2].
Why and how does the pineal gland become calcified?
The pineal gland demonstrates the highest susceptibility to calcification among all organs/tissues of human body. There are several proposed mechanisms for pineal gland calcification.
Membrane debris buildup
Tryptase-releasing mast cells
Ca2+-ATPase signaling breakdown
Mesenchymal stem cells (MSCs) differentiation
Environmental insults such as fluoride
The first is the metabolic theory of pineal calcification, which deems it a normal process. Calcium binding triggers the exocytosis of polypeptide vesicles. This calcium is exchanged and deposited. Extracellular membrane debris, a by-product of pineal neuronal and glial polypeptide exocytosis, forms the seed crystals that build up into calcification over time[1].
The second theory has to do with mast cells and tryptase. During systemic or local pathological conditions, tryptase-containing mast cells infiltrate the pineal gland and release bioactive compounds like tryptase that participate in calcification.
The third mechanism involves a breakdown of calcium signaling, associated with aging and pathology. Due to failure of the Ca2+-ATPase, there is high intracellular calcium, which results in calcium elimination from pinealocytes.
The fourth theory proposes that the pineal gland has a blood filtration function like the kidney. The pineal gland has the highest blood flow percentage of any organ in the body besides the kidneys. Pineal concretions resemble enamel and dentine in their calcium-phosphate molar ratio. Formation may be organized and programmed. Melatonin facilitates capacity of MSCs to differentiate into osteoblast-like cells. Melatonin upregulates bone morphogenic protein (BMP-2) and alkaline phosphatase (ALP), and facilitates osteoblast proliferation, mineralization, and bone formation.
MSCs can be triggered by:
Chronic vascular inflammation and increase in pro-inflammatory cytokines, like TNF-a and IL-22
Brain tissue hypoxia caused by hypertension, sleep apnea, stroke, or respiratory disorders
Intracranial pressure caused by idiopathic intracranial hypertension, brain trauma, stroke, or AD
Finally, environmental biohazards contribute to calcification, including fluoride. Fluoride is often used for aesthetic reasons but can negatively affect systemic health. High levels of fluoride causes pineal calcification and has been shown in dozens of studies to lower IQ[12]. Major sources of fluorine ions or compounds include toothpaste, tap water, and PFOAs in non-stick pans. Thus, decrease in environmental fluoride pollution can delay or avoid premature pineal calcification[2].
How to activate the pineal gland
1. Avoid fluoride and PFAS
Avoid fluoride-containing toothpastes. Tom's of Maine and Desert Essence offer fluoride-free toothpastes.
Filter your water. Reverse osmosis, deionization, and distillation can remove about 90% of fluoride, but activated carbon filters (e.g. Brita) cannot. Keep in mind that reverse osmosis also removes beneficial minerals from water. Learn more about the best water purification methods.
Avoid cooking with non-stick pans. They contain perfluoroalkyl substances (PFAS) like Teflon. PFAS have been called "forever chemicals" because sun, microbes, and heat don't break them down. PFAS are biopersistent, staying in the body for long periods of time, and have been associated with kidney, pancreatic, and testicular cancer.
Instead, cook with stainless steel or cast-iron skillets. PFOAs can also be found in microwave popcorn bags.
Avoid products with PFAS. According to an EWG Skin Deep scientific report, PFAS were found in cosmetics, sunscreen, moisturizers, anti-aging products, and men's shaving cream.
A study of nearly 70,000 people near a Teflon plant in West Virginia linked PFOA in tap water to kidney and testicular cancer, thyroid disease, high cholesterol and other health problems. From WebMD, PFOA causes testicular and kidney cancer, immune system problems, liver damage, ulcerative colitis, and changes in blood pressure during pregnancy. It also disrupts hormones and reproduction. Robust data exist to link PFAS with obesity, diabetes, reduced semen quality, and polycystic ovary syndrome.[16]
Avoid endocrine-disrupting chemicals. Similar associations exist for exposure to bisphenol A, widely used in plastics, and for organophosphate pesticides. Phthalates, present in hundreds of products, including vinyl flooring, soaps, and shampoos, have also been linked to reproductive disorders.
PFAS are found virtually everywhere, including bag popcorn, coating on furniture, and Patagonia clothing. Clorox, Scotchgard, Act, and Glide floss all contain materials sold by 3M and DuPont. PFAS can also be found in water repellent outerwear and stain-proof carpeting, so be sure to do your research before purchasing these products. PFAS bioremediation is still an area of exploration (Tseng, 2012).
Teas: Avoid bottled teas like Nestea, Lipton, and Arizona, which contain fluoride levels deemed unsafe. Look for organic, unbleached bags, microplastic-free teas.
2. Eat a nutritious diet
Get calcium through the diet by eating spinach, kale, broccoli, sesame seeds, chia seeds, and quinoa.
Herbs: Milk thistle is a powerful antioxidant that helps with liver function and heavy metal removal. Moringa is a natural water filter. Chaga mushrooms, called the "diamond of the forest" in Japan, are rich in melatonin and melanin. Algae like spirulina can remove heavy metals and boost oxygen and immune function. Shilajit and raw cacao are also beneficial.
Consume turmeric, which contains curcumin. Curcumin has been found to attenuate the neurotoxic effects of fluoride, improving neuronal cell viability in mice[13].
Eat organic. Fluoride-containing pesticides like cryolite and sulfuryl fluoride are widely used on many berries, cruciferous veggies, grapes, wine, kale, eggplants, nectarines and peaches, peppers, and tomatoes.
Vitamins D3, K2, and B12 are helpful for the pineal gland. Vitamin K2 promotes bone calcification and prevents calcification in blood vessels and kidneys. Vitamin K rich foods include kale, brussels sprouts, asparagus, blueberries, scallions, cucumbers, dried basil, parsley, kiwi, avocados, chives, arugula, dandelion greens, spinach, beef liver, and swiss chard. B12 promotes pineal melatonin production.
Reduce refined sugar, flour, and vegetable oil, which can cause inflammation.
3. Regulate your light exposure
Spend at least 10-30 minutes in sunlight every day without sunglasses. Reduce blue light exposure in the evening, as melatonin secretion starts around 9pm. At minimum, turn off screens an hour before bed. Finally, sleep in complete darkness.
4. Activate your vagus nerve
Meditation, yoga, and deep breathing exercises can stimulate the vagus nerve, a major part of the parasympathetic nervous system. Keeping your tongue at the roof of your mouth also activates the vagus nerve and enhances relaxation.
5. Avoid aluminum exposure
Since aluminum is a confirmed neurotoxin, it was found in pineal gland crystals, and both are associated with neurodegeneration, it is very important to monitor the intake of this element. Be sure to fully weigh the risks and benefits before using aluminum-containing products on and in your body, such as deodorants, antacids, and some vaccines, as well as dietary sources of aluminum, such as fish and contaminated water.
6. Fasting
A chronic 40% reduction in caloric intake beginning at a young age extended the lifespan of mice, rats, dogs, and monkeys by some 30-50%. Old, ad libitum fed rats suffered from tumors and cataracts, while chronically undernourished rats appeared to be in good health until a very old age. The food-restricted rats had nighttime melatonin levels twice as high as their ad libitum counterparts due to twice the number of adrenergic receptors in the pineal gland[14].
7. Try grounding, Earthing, or forest bathing
Rubber and plastic soled shoes insulate us from charge transfer with the Earth. Walking barefoot, particularly after a thunderstorm, provides electrons from the ground, which neutralizes free radicals that drive oxidative stress, inflammation, and aging. Contact with the ground resulted in better sleep[15].
Earthing, also known as forest bathing, synchronizes our electrical and circadian rhythms. It literally grounds us with the electromagnetic frequency of the Earth.
Some other ways to ground include sitting on the grass, meditating under a tree, touching a tree, reading a book on a towel, and walking barefoot on the beach.
8. Listen to your high-performance music
Music has a powerful influence on human brain activity. Certain frequencies, timed rhythmically, can entrain brain activity and induce transcendental states and deep awareness of the present. Try listening to the music you usually opt for during meditation, relaxing walks in nature, or studying, such as classical music, jazz, chillstep, or acoustic instrumentals.
Key takeaways
The pineal gland lacks a blood-brain barrier, leaving it prone to calcification, which affects most adults.
Melatonin promotes DNA repair and protects against epigenetic modifications and liver toxicity by environmental insults such as herbicides and cigarette smoke.
Pineal gland calcification is associated with aging, vascular inflammation, brain hypoxia, and neurodegeneration.
Fluoride, found in many toothpastes and tap water, and PFOAs, found in non-stick pans and microwave popcorn, can contribute to pineal gland calcification.
Sunlight, certain foods, meditation, and minimizing screen use at night can promote pineal gland health.
This was part three of a three-part series on the pineal gland:
References
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Tan, D.X., et al., Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland. Molecules, 2018. 23(2).
Yalcin, A., et al., Age and gender related prevalence of intracranial calcifications in CT imaging; data from 12,000 healthy subjects. J Chem Neuroanat, 2016. 78: p. 20-24.
Ozlece, H.K., et al., Is there a correlation between the pineal gland calcification and migraine? Eur Rev Med Pharmacol Sci, 2015. 19(20): p. 3861-4.
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Kleszczynski, K., et al., Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT-1 melanoma cells. J Pineal Res, 2019: p. e12610.
Shafabakhsh, R., et al., Melatonin: A new inhibitor agent for cervical cancer treatment. J Cell Physiol, 2019. 234(12): p. 21670-21682.
Song, J., et al., Downregulation of AKT and MDM2, Melatonin Induces Apoptosis in AGS and MGC803 Cells. Anat Rec (Hoboken), 2019. 302(9): p. 1544-1551.
Hu, C., et al., Protective role of melatonin in early-stage and end-stage liver cirrhosis. J Cell Mol Med, 2019.
He, Y.T., et al., Melatonin protects against Fenoxaprop-ethyl exposure-induced meiotic defects in mouse oocytes. Toxicology, 2019. 425: p. 152241.
Wang, X., et al., Melatonin alleviates cigarette smoke-induced endothelial cell pyroptosis through inhibiting ROS/NLRP3 axis. Biochem Biophys Res Commun, 2019. 519(2): p. 402-408.
Nakamoto, T. and H.R. Rawls, Fluoride Exposure in Early Life as the Possible Root Cause of Disease In Later Life. J Clin Pediatr Dent, 2018. 42(5): p. 325-330.
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Chevalier, G., et al., Earthing: health implications of reconnecting the human body to the Earth's surface electrons. J Environ Public Health, 2012. 2012: p. 291541.
Paul M Stewart et al., Environmental Pollution, Climate Change, and a Critical Role for the Endocrinologist. Journal Clin Endocr & Metab, 2021. 106(12): p. 3381–3384.