ABSTRACT
This article provides a detailed review of the association of major depression with coronary heart disease (CHD), examines the biological variables underpinning the linkage and discusses the clinical implications for treatment. When considering the co-morbidity between major depressive disorder (MDD) and CHD it is important to differentiate between (i) the prevalence and impact of MDD in those with existing CHD and (ii) MDD as a risk factor for the development of CHD. Whether the same biological mechanisms are at play in these two instances remains unknown. Depression is common in patients with CHD. Importantly, depression in these patients increases mortality. There is also consistent evidence that MDD is a risk factor for the development of CHD. The relative risk of developing CHD is proportional to the severity of depression and is independent of smoking, obesity, hypercholesterolaemia, diabetes mellitus and hypertension. There is a clear need to identify the underlying neurochemical mechanisms responsible for MDD and their linkage to the heart and vascular system. Of particular interest are activation of stress pathways, including both the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, and inflammatory-mediated atherogenesis. Elevated sympathetic activity, reduced heart rate variability and increased plasma cortisol levels have been documented in patients with MDD. In addition to direct effects on the heart and vasculature, activation of stress pathways may also be associated with increased release of inflammatory cytokines such as interleukin-6 and tumour necrosis factor-alpha. Elevated levels of C-reactive protein are commonly observed in patients with MDD. The majority of investigations examining treatment of depression following myocardial infarction have focused on safety and efficacy; there is little evidence to indicate that treating depression in these patients improves survival. Given that strategies for preventive therapy remain incompletely formulated, future research should focus on generating a better understanding of the neurobiology of MDD and heart disease as a basis for rational and effective therapy.

NEW FACTS AS PhD's GET BUSY
What you're about to read will come as a surprise - in many it will understandably generate anger. It took me 10+ hours of digging through historical records and filed patents to get this information. If you keep reading you'll see how one could easily make the argument that adding fluoride to our water was motivated by a lot more than just better bones and teeth.

POISON IN THE AIR
To begin, for many years I taught behavior and emotionally disturbed children in the Florida Public School system. After that I studied Public Health & Toxicology at the University of South Florida. To get to the college I'd drive from my home in Vero Beach, FL to the city of Tampa. During this 3 hour trip I'd travel through a small town just south of Lakeland - for the next several miles the smell was anything but pleasant - disgusting pretty much sums it up. Later I discovered it was coming from an industrial complex making an ingredient for chemical based fertilizer.

THE FERTILIZER LABEL
When you buy fertilizer at Walmart or wherever, you'll typically see three numbers on the label separated by a dash. One of the most common is your typical 6-6-6 fertilizer (Their choice of triple 6's seems appropriate). The first number represents the percent of nitrogen while the last number represents the percent of potassium. However, that middle number? That's the Gremlin and represents the percent of phosphate. In fact, deep pit mines in central Florida are one of the biggest sources of phosphate.

PHOSPHATE IS HARD TO GET... BUT...
When getting the materials for the middle fertilizer number, the first step is to dig up rock beneath the ground called rock phosphate. It's then pulverized into a powder and transferred to a facility for a unique process discovered by chemists working for the industry.

At this point, sulfuric acid is poured through the rock phosphate - which causes the liquid gold known as phosphoric acid (our middle fertilizer number) to drain away from the rock powder and be collected. Unfortunately, a bit of a nightmare arose while doing this in the early years.

DEAD COWS - DEAD CITRUS
Back in the 1950s and 60s there was no EPA, and therefore, no restrictions. Basically the Wild West for the chemical industry - meaning they could pretty much do whatever the Hell they wanted.

You see, it turned out that pouring sulfuric acid through phosphate rock also created highly toxic fluoride gases. These poisons would rise up smokestacks and then travel miles downwind, eventually settling on pastures and agricultural areas.

Each year this continued resulted in more fluoride landing on soil and more fluoride being taken up by plants and animals. Eventually, reports started coming in of cattle falling to their knees and unable to walk. Bones were misshapen and ranchers noticed cattle had a dark brown staining on their teeth. It wasn't long until tens of thousands of cattle were reported dead. But not just cattle, the agricultural landscape was being poisoned as well, with thousands of acres of citrus dying from diseases that were never a problem before. - Something unnatural was going on....

Eventually, someone figured it out - the fertilizer company producing phosphoric acid was basically killing everything around it. Of course, the citrus and cattle industries weren't small players in Florida, ensuring this newly invented fertilizer poison had to be stopped.

NEW INVENTION CHANGES EVERYTHING
With dreams of dollar $igns floating about - here's the question fertilizer industry chemists pondered... How do we get this dog-gone phosphoric acid out of the rock without killing all life around us?

From this engineering challenge came a fascinating new invention called - The Wet Scrubber. This device provided a way to capture and prevent the toxic fluoride gases from floating up up and away - but at a cost that wouldn't be realized for decades. The Wet Scrubber process was improved and a patent was given to Exxon/Mobile for their new and exciting fluoride removal process (Patent # US4175944A). Here's how it works.

Rather than pour sulfuric acid over the rock powder out in the open, the machine allowed for this to be done inside an enclosed metal containment system. Sulfuric acid was still pushed through the rock phosphate like before, but this time, when the toxic fluoride gases rose, they were funneled into another enclosed area. Here, the gases were heated with ammonia and then treated with a high pressure spray solution containing various chemicals.

The fluoride gases would then combine with the liquid and - Wallah! No more fluoride gas in the air. It was now all in the liquid. This newly formed toxic soup was then drained out and put into large storage containers with a nice big label saying "WARNING - Hydrofluorosilicic Acid."

ANOTHER FINE MESS OLLIE...
Even with this new Wet Scrubber invention, the fertilizer and chemical industry were again in a pickle. Turns out this concentrated liquid fluoride they created was so highly toxic that it was literally labeled a "Hazardous Waste" and therefore, could not be dumped into rivers or stored in ponds onsite. Something else had to be done.

INGENIOUS!
Some chemists in the fertilizer industry were apparently aware of several studies showing small amounts of natural fluoride could strengthen bones and teeth, and possibly reduce cavities. Since that research was out there, maybe the public would buy the idea that if a little fluoride was good, then more would be better? That's actually an ingenious strategy if you think about it and appears to have worked - as fluoride was quickly added to the majority of water supplies in the U.S. Not only in water, today it is found in everything from food - to bottled water- to toothpastes - to your favorite can of soda or beer.

EVIDENCE FOR THE TICKING TIME BOMB
After 70 years of the U.S. publics' digestive track assisting the fertilizer industry in getting rid of a toxic hazardous waste - what have we learned?

For one - just like smoking cigarettes or shooting crack, it can take decades for low levels of a poison to cause enough damage and genetic alterations for health problems to appear (they call this epigenetic damage).

This is especially true with fluoride since (unlike other toxins) it slowly accumulates inside your cells day after day - and not just in your bones and teeth. Studies coming out just recently show it also accumulates in your liver, kidneys, colon and even inside your brain and heart. Scientists understand this delayed accumulation effect and explains why there has been a surge of new medical studies investigating the safety of fluoride (with many coming out since 2020.

ABSTRACT
Fluoride mediated disruption of sex steroid hormones has been demonstrated in animals. However, evidence from humans was limited and contradictory, especially for children and adolescents. Based on data of the National Health and Nutrition Survey (NHANES) 2013–2016, a total of 3392 subjects aged 6–19 years were analyzed in this cross-sectional study. Both plasma and water fluoride levels were quantified electrometrically using the ion-specific electrode. Sex steroid hormones of total testosterone, estradiol and sex hormone-binding globulin (SHBG) were tested in serum. Percent changes and 95% confidence intervals (CIs) in sex steroid hormones associated with tertiles of fluoride levels (setting the first as reference) were estimated using adjusted linear regression models by stratification of gender and age. Compared with subjects at the first tertile of plasma fluoride, percent changes (95% CIs) in testosterone were −8.08% (−17.36%, 2.25%) and −21.65% (−30.44%, −11.75%) for the second and third tertiles, respectively (P trend <0.001). Male adolescents at the third tertile of plasma fluoride had decreased levels of testosterone (percent change = −21.09%, 95% CIs = −36.61% to −1.77%). Similar inverse associations were also found when investigating the relationships between plasma fluoride and estradiol. Besides, the data indicated decreased levels of SHBG associated with water and plasma fluoride among the male adolescents (percent change of the third tertile = −9.39%, 95% CIs = −17.25% to −0.78%) and female children (percent change of the second tertile = −10.78%, 95% CIs = −17.55% to −3.45%), respectively. The data indicated gender- and age-specific inverse associations of fluoride in plasma and water with sex steroid hormones of total testosterone, estradiol and SHBG in U.S. children and adolescents. Prospective cohort studies are warranted to confirm the causality.

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ABSTRACTThis study provides diverse lines of evidence demonstrating that fluoride (F) exposure contributes to degenerative eye diseases by stimulating or inhibiting biological pathways associated with the pathogenesis of cataract, age-related macular degeneration and glaucoma. As elucidated in this study, F exerts this effect by inhibiting enolase, τ-crystallin, Hsp40, Na+, K+-ATPase, Nrf2, γ -GCS, HO-1 Bcl-2, FoxO1, SOD, PON-1 and glutathione activity, and upregulating NF-κB, IL-6, AGEs, HsP27 and Hsp70 expression. Moreover, F exposure leads to enhanced oxidative stress and impaired antioxidant activity. Based on the evidence presented in this study, it can be concluded that F exposure may be added to the list of identifiable risk factors associated with pathogenesis of degenerative eye diseases. The broader impact of these findings suggests that reducing F intake may lead to an overall reduction in the modifiable risk factors associated with degenerative eye diseases. Further studies are required to examine this association and determine differences in prevalence rates amongst fluoridated and non-fluoridated communities, taking into consideration other dietary sources of F such as tea. Finally, the findings of this study elucidate molecular pathways associated with F exposure that may suggest a possible association between F exposure and other inflammatory diseases. Further studies are also warranted to examine these associations.