Social and Miscellaneous Topics
By: Jonathan Kahan MD
What you need to know
The evidence for this section of the book is less certain, as social aspects of life are never in isolation and supplements/non cardiac pharmacology studies tend to be smaller, newer and less established. However, making some of these changes can have an outsized impact on your life and health.
There is a metabolic component to mental health
Supplements should be used as the “tip of the spear”, and correcting for the other conditions in this book should be prioritized.
Cell phones, screens and social media are the “processed food” of social interaction and removing them from your life is excellent for your overall well-being.
Find a purpose higher than yourself, get out in nature, and have real face to face interactions.
What about mental health? What does mental health have to do with cardiology?
Metabolic dysfunction – particularly at the mitochondrial level – may be a foundational element of neuropsychiatric disorders.39,44 Mitochondria are the powerhouse of all cells and the brain is the organ that uses the most energy, therefore it makes sense that mitochondrial metabolic dysfunction is tightly correlated with depression, anxiety, bipolar, schizophrenia etc. Mechanistically, high blood pressure, obesity, smoking, diabetes, lack of exercise, poor sleep and metabolic syndrome cause inflammation (see smoking, hypertension, obesity, exercise chapters). These inflammatory markers (IL-1, IL-6 etc) lead to dysregulation of the mitochondria in the synapses of the brain (in all cells really) leading to dysfunction and cell death.
Clinically the results are striking. Insulin resistance (IR) is a major risk factor for depression; moderate increases in IR ratio correlated with 89% higher incidence of major depression41. Low grade inflammation is common in depression, bipolar disorder, schizophrenia and even autism.40 Metabolic syndrome doubles the risk of cognitive decline and dementia.42 Similar results have been shown across the spectrum of primary prevention cardiology!
Furthermore, our “second brain” (the gut microbiome) are constantly signaling through the bidirectional gut-brain axis. Patients with depression have a less diverse gut microbiome and even certain species are correlated with anxiety and stress related disorders. Serotonin, GABA and short chain fatty acids are largely stored in our gut, and further our gut can modify tryptophan metabolism and have a profound effect on our mood.43
All of this leads to proof of a metabolic root cause for psychiatric disorders, in addition to substances like alcohol and behaviors like social media use, being a core driver of poor mental health in America.
Figure showing relationship between cardiovascular/metabolic conditions, substances and the gut brain axis and mental health outcomes such as anxiety and depression.
The good news is that by framing mental health from the lens of primary prevention cardiology, we can pull on low hanging fruits such as diet, exercise, good sleep, fiber etc. In other words, the topics in this book apply to the treatment of both!
****Caveat: Just as in cholesterol, blood pressure etc., psychiatric conditions that present as more severe will likely require pharmacology in addition to the above. As always, consult with your mental health physician in addition to the recommendations in this book*****
What about supplements in general?
Supplements in general should be used as the tip of the triangle of cardiovascular health (see image below), and should not be used front line in the pursuit of CVD prevention. Only after the social, physical, diet, sleep and other health metrics are optimized for should supplements enter the picture. You have much more control over a sense of purpose and exercising than you do over what supplements will do to your body (no premarket efficacy and safety approvals, lack of or underdosed active ingredients as advertised, undeclared substances, lack of human trials).45-47
Figure 1. At the base of the triangle is purpose (see below), which we have the most control over. As we move up the triangle our control becomes less and less. For example, you can control going to the gym much more easily than you can control an external stress, such as a family emergency..
What about protein powder?
Protein powder comes in a variety of forms, the most beneficial version from a cardiovascular disease standpoint is whey protein from eggs/dairy. Whey is superior to plant protein powder as it contains a variety of amino acids not found in the plant form. The effects of protein powder have been shown to be beneficial in a variety of cardiovascular conditions including high blood pressure, type II diabetes, cholesterol, endothelial function, and even inflammation. Protein powders are absorbed rapidly, typically within 30-45 minutes. Note that you can only absorb 25-30 grams of protein per meal, and with whole food that absorption takes 3-4 hours1. Therefore, protein powders represent an excellent way to get to our recommendation of 1 gram per pound of ideal body weight daily.
Note that in healthy patients, the concern for kidney issues with a higher protein diet is minimal. Note also that if you have trouble obtaining this goal, you can take a scoop of protein powder in your fasting window to make it up, as this is more of a priority than the calories ingested from the protein itself. Lastly note that muscle is receptive to protein over 24 hours after exercise, and it is not crucial to consume a high protein meal immediately after exercise.
What about creatine?
Creatine is dosed typically at 5 grams/day and is available OTC. It is used by athletes to improve strength and high intensity exercises and may aid in recovery. There is limited evidence of improvement in conditions such as congestive heart failure (the heart is a muscle) and ischemic heart disease2. One concern is that it leads to water retention which may increase blood pressure. However, the benefits of creatine neurologically likely outweigh any risks (there is extensive data on this). We recommend checking with your physician to see if creatine supplementation is the right option for you.
What about Vitamin C Supplementation?
Vitamin C has been shown to improve endothelial function (even at lower doses of 500 mg) and modest reduction in blood pressures (at higher doses of 2000 mg)7. Ascorbic acid (the most common vitamin C formulation) blood levels were shown to be inversely correlated with all-cause mortality and cardiovascular mortality. We recommend taking 500-1000 mg of vitamin C daily. Food sources are always best, in this case red bell peppers, citrus fruits, strawberries and broccoli. If you cannot obtain these there are OTC supplements.
What about vitamin D supplementation?
Vitamin D is the worst named vitamin of all the common ones. It is a steroid hormone involved in multiple processes and pathways in the body. Humans can produce vitamin D through sunlight (note there are increased cardiovascular events in winter and further from the equator), food (sardines/fatty fish are the best source) or by supplementation. It is also genetically determined. Vitamin 25-OH D deficiency is defined as < 20 ng/mL, insufficiency 20-40 ng/mL, optimal approx. 40-60 ng/mL and too high being >80 ng/mL, In the NHANES trial, 68% of white, 88% of Hispanic and 97% of black patients were deficient in Vitamin D8,9. Vitamin D mainly comes from sunlight exposure on skin, sardines, salmon, mackerel. OTC supplements are available and cheap. Dosing varies and we aim more to obtain optimal blood levels consistently. Note there is a prescription version of Vitamin D you will need to obtain if your blood levels are low enough (ask your physician). Vitamin D is involved in regulation of the renin-angiotensin system, which is one of the main regulators of blood pressure, and adequate vitamin D levels can lead to improved blood pressure10. It has anti-inflammatory effects (inflammation is a key driver of atherosclerosis aka plaque in the arteries) as well as calcium regulation which is key for cardiac function and vascular compliance. Lastly, while outside the scope of this book, the VITALS trial showed significant improvement in cancer all-cause mortality after one year latency in patients who had adequate vitamin D11.
What about magnesium supplementation?
There are a multitude of magnesium supplements available, with magnesium chloride/glycinate (for premature extra ventricular contractions and cardiovascular health) and magnesium oxide (for gastrointestinal health) having the best absorption. The dose is 400 mg to 800 mg daily and is available OTC12. Magnesium helps stabilize heart rhythms, and high dietary magnesium was associated with lower cardiovascular mortality, congestive heart failure, blood pressure and stroke13. While magnesium can easily be measured in serum, with a goal level of 1.7-2.2 mEq/L, it is important to note that 99% of magnesium is sequestered in bone/cells, with serum levels only representing 1%. Therefore, occasionally testing red blood cell (RBC) magnesium levels, looking for deficiency symptoms and risk factors such as muscle cramping, arrhythmia, irritability, and gastrointestinal/kidney disorders and medication uses (antibiotics, diuretics etc.). Data on Magnesium threonate is mixed at this time, while it does cross the blood brain barrier, the trials in humans used a combination of supplements such as vitamin D14,15. This version of magnesium is classically used for sleep and to restore neurologic deficits.
What about Urolithin A?
Urolithin A, a gut-derived metabolite of ellagitannins (found in pomegranates and certain berries), has garnered growing interest for its potential cardioprotective properties. Preclinical evidence suggests that urolithin A can help mitigate atherosclerosis, reduce vascular inflammation, and improve endothelial function—factors instrumental in the prevention and management of cardiovascular disease (CVD). Its ability to promote mitophagy (the selective degradation of damaged mitochondria) may further enhance cellular energy efficiency and reduce oxidative stress. Although several animal and cell-based studies show promising results, data from human trials focusing specifically on cardiovascular outcomes remain limited. Early-phase clinical research has demonstrated the safety of urolithin A and hinted at broader health benefits (such as improved muscle function and reduced inflammation), suggesting a possible indirect benefit to cardiovascular health. However, larger-scale and longer-term randomized controlled trials are needed to clarify whether these preliminary findings translate into meaningful reductions in CVD events and mortality.49,50
What about homocysteine?
Homocysteine is an amino acid in blood that is elevated when patients are deficient in vitamin B12. A large proportion of the population have MTHFR gene mutations and are unable to absorb vitamin B12 in its native form16. This can be tested in blood and the treatment is to take methylated B12, which can be purchased OTC. In theory homocysteine may contribute to CVD by potentially damaging blood vessels, however studies at this time have shown a more limited role of homocysteine levels and cardiovascular disease17.
What about uric acid?
Elevated uric acid, which comes more from fructose sugar and alcohol than red meat, is a potential risk factor for CVD. It has been linked to hypertension, congestive heart failure, stroke and coronary artery disease through endothelial dysfunction and oxidative stress/inflammation. However, direct treatment of uric acid with medications such as allopurinol did not show a reduction in CVD (ALL-HEART Trial)35. Therefore, while uric acid is a useful marker for CVD risk, treating the underlying cause of the elevated uric acid (eg. lowering fructose intake) will be the most beneficial to preventing CVD rather than the uric acid itself.
“From the mightiest pharaoh, to the lowliest peasant, who doesn’t enjoy a good sit?”. -Mr. Burns, The Simpsons.
Sitting is largely viewed as idle, neutral time. It is not. Occupational sitting has been shown across numerous studies to be related to increased (16%!) all cause cardiovascular mortality and worsening (34%) outcomes across the board, even among physically active individuals34. The results were mitigated by an extra 30 minutes of activity per day (in addition to what athletes were already doing). Other ways to mitigate occupational sitting is to use a standing desk or a pedal bike/treadmill under the desk. Note also that the studies looked at occupational sitting only, relaxing at home is fine!
What about meditation?
Meditation has been shown to improve blood pressure, heart rate variability (variation in time between heart beats, the higher the better), reduced stress/anxiety and inflammation and a 2017 meta-analysis showed it may reduce the risk of hypertension and stroke18. Various forms of meditation have been shown to help including mindfulness meditation, transcendental meditation, yoga etc. Most studies examined regular practice usually daily with 10-30 minutes a day. We recommend some form of meditation for most people, however, persistent meditation associated side effects run in the 10% range (we bet you didn't know there were any side effects)19! Most common side effects were anxiety, trauma re-experience and emotional instability, with childhood adversity increasing the risk of side effects. Hyper arousal and dissociation also occurred persistently at approximately a 10% rate. It is important to balance the benefits of meditation with potential side effects, especially if you have childhood traumas.
What about daily stress aka chronically elevated cortisol?
When we discuss stress, we mean chronic, everyday stress that is detrimental to your health. Short term stress, such as exercise, performing a difficult task or challenges are very beneficial. Chronic stress can lead to hypertension, elevated calcium scores increased risk of heart attack and strokes secondary to prolonged elevation of stress hormones such as cortisol and adrenaline33,48. It is difficult to control the external factors that lead to stress, and therefore increasing your resilience (ability to adapt, recover and overcome) towards stress should be the focus. We almost called this book “The Resilience Manual” since the topics covered overlap identically. Focus on diet, exercise, sleep and the social topics discussed in this book, and you will see how the stress levels begin to resolve themselves.
What about microplastics?
A very important study published in the New England Journal of Medicine in demonstrated the dangers of microplastics (tiny plastic particles <5 mm in diameter) from a CVD standpoint3. Three hundred patients had their carotid plaques removed surgically and examined for microplastics, which appear as jagged edges of debris with surrounding inflammation. Patients who had microplastics detected were at a significantly higher risk of heart attacks, strokes and all cause mortality by 353%! The main way that microplastics enter our bodies is by ingestion of food and liquid. Drinking water, both plastic bottled and tap, can contain significant amounts. We recommend installing a reverse osmosis filtration system or other filter systems to prevent ingestion and to avoid all liquids that are in plastic bottles (especially those stored on shelves)4. Note most fridge filters do not remove microplastics. Drinking exclusively from non-plastic containers should also be pursued. Note hot food or liquid can microscopically melt all plastics (regardless of type), and therefore avoid using plastic containers when food/liquid is hot. For example, plastic cutting boards washed in a dishwasher lead to the consumption of 12 credit cards worth of plastic annually! Paper coffee cups/aluminum cans actually are lined with plastic to prevent spillage as are most coffee makers (especially pods). Therefore, we recommend getting a stainless steel only coffee maker/kettle. Shellfish accumulate more microplastic than any other food source. This is an area of ongoing research.
What about metformin?
Metformin is an oral diabetic medication that blocks the production of glucose in the liver, stimulates glucose uptake in muscle, and blocks sugar absorption32. It also inhibits mitochondrial production of energy. It may help with weight loss or is weight neutral. In 2018 there was excitement about its longevity effects, however this did not pan out in subsequent twin studies. Metformin remains a mainstay in the treatment of patients with diabetes and is often the first line agent prescribed.
What about SGLT-2 Inhibitors?
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of medications that are mainly used in type 2 diabetes by preventing glucose reabsorption from the kidneys, resulting in excretion in the urine. SGLT2 inhibitors are showing a lot of promise in the arena of primary cardiovascular prevention5. They decrease the epicardial (visceral) fat around the heart (epicardial fat is associated with negative outcomes in cardiovascular longevity)6. In trials they have been shown to lower rates of cardiovascular death or hospitalizations secondary to congestive heart failure. While these studies were performed in diabetic patients, there are significant advances in studies for non-diabetic patients, warranting a closer look at SGLT-2 inhibitors as a mainstay of cardiovascular prevention in the future.
What about testosterone replacement therapy?
Low testosterone (total testosterone < 300 ng/dL) in adult men can manifest through decreased libido, fatigue, reduced muscle mass, erectile dysfunction, mood disturbances, and difficulties with concentration. The TRAVERSE trial—a large, randomized, double-blind, placebo-controlled study of over 5,000 men with or at high risk for cardiovascular disease—found that testosterone therapy did not significantly increase the incidence of major adverse cardiovascular events, (although it did significantly raise blood pressure), suggesting that, in appropriately selected patients, it may be relatively safe from a cardiovascular standpoint36. Beyond exogenous testosterone replacement, other treatment approaches include lifestyle interventions (e.g., weight loss [fat cells convert testosterone into estrogen!], increased physical activity, and adequate sleep), as well as therapies that stimulate the body’s own testosterone production, such as selective estrogen receptor modulators (e.g., clomiphene citrate).
What about estrogen replacement therapy?
Estrogen replacement therapy (ERT) effectively alleviates menopausal symptoms such as hot flashes, night sweats, and bone density loss. However, major studies have raised concerns about cardiovascular (CV) risk. The Women’s Health Initiative (WHI) combined-therapy arm in 16,608 postmenopausal women found elevated risks of coronary heart disease37. Meanwhile, the Heart and Estrogen/progestin Replacement Study (HERS) reported no overall cardioprotective benefit of combined hormone therapy in women with established coronary disease with an increased risk of stroke38. Critics point out that therapy in these trials was often started long after menopause began, whereas starting ERT earlier might produce different CV outcomes (the “timing hypothesis”). Additionally, only specific hormone formulations were tested (e.g., conjugated equine estrogen plus medroxyprogesterone acetate), limiting generalizability to other regimens. These critiques have led to more nuanced guidelines, emphasizing individualized treatment, the lowest effective doses, and careful attention to the timing of therapy initiation.
The bottom line is at the time of this writing, we just don’t know the CVD risks of ERT.
What about dental health?
Inflammation can occur in the gums and teeth, which can be detected on bloodwork and therefore in theory can lead to cardiovascular disease. In fact poor dentition has been shown to correlate with cardiovascular disease. However, treating isolated inflammation from the oral cavity has not shown as of yet to significant outcomes in terms of cardiovascular health. Regardless, oral health is essential for several reasons such as pain avoidance, being able to eat the foods you want, avoidance of dental procedures in the future, and overall lifestyle, health and wellbeing, especially as we age. Note also that children are having more dental procedures/braces over generations secondary to lack of chewing as a result of processed food30. Therefore, we recommend in addition to an unprocessed diet, avoid acidic drinks (also an ultra-processed food), brush teeth twice daily for 2 minutes each, floss regularly and see your dentist!
What about mTOR inhibitors/longevity medications?
Are there substances that, when given to healthy individuals, expand lifespan beyond what would be normal? This is the area of longevity medicine. The mammalian target of rapamycin (mTOR) is a signaling protein that is central to several key cell processes including growth and proliferation, nutrient sensing (via amino acids), growth factor sensing (like insulin), autophagy (programmed cell death) and lipid metabolism (for cell membranes)20. There are two mTOR inhibitors that are emerging in the literature as potential potent cardiovascular and longevity enhancers.
The first is Quercetin which is OTC and found in fruits, vegetables, teas and red wine. Quercetin is a flavonoid that inhibits mTOR, is a potent antioxidant, improves blood sugar (enhances GLUT4 in muscle cells), increases nitric oxide (which reduces blood pressure), and enhances endothelial function. Typical doses are 500-1000 mg daily, and typically enhanced absorption with vitamin C or Bromelin21.
Rapamycin (aka sirolimus) was discovered as an antibiotic on Easter Island and is commonly used in immunosuppression for transplants. However, taking intermittent dosing (it is by prescription only), appears to inhibit mTOR complex 1 without affecting complex 2 (which carries most of the side effects)22. Rapamycin has been shown to enhance longevity in mouse models by up to 30% (when mice took in middle age). Rapamycin in humans has shown to improve immune function and chronic inflammation. As aging is the most common risk factor for all cardiovascular disease, it remains to be seen whether medications like mTOR inhibitors will play a role in cardiovascular disease prevention.
At this time, it is unclear whether this class of supplement/medication will lead to improved cardiovascular outcomes, although the class appears promising and worth watching in the future. Note also at this time, NAD/NMN boosters have not shown significant longevity outcomes in mammals, though research is ongoing23.
What about substances that increase nitric oxide?
Beetroot juice, L-arginine and phosphodiesterase-5 (PDE-5) inhibitors (sildenafil aka Viagra, tadalafil aka Cialis) all increase nitric oxide concentration, which leads to vasodilation and significant drops in blood pressure. Furthermore, the PDE-5 inhibitors may improve endothelial function and enhance cardiac contractility. Indeed, studies have shown improvement in major adverse cardiovascular outcomes and all-cause mortality in men with erectile dysfunction using PDE-5 inhibitors30. The downside is potential severe hypotension (low blood pressure), which may be fatal. Further studies are needed, however this is another area of promising research in the field of primary prevention for cardiovascular health.
What about self experimentation?
Throughout this book, we have tried to provide the most up to date and evidence based primary prevention tools possible. These will work for the majority of you but not everyone, even if the science behind the recommendation is iron clad. For example, we recommend almonds in the obesity chapter, however this particular author cannot handle them, and will eat an entire 5 lbs bag if given the chance. Therefore, especially if something is off in your diet, sleep, mood, exercise etc., we recommend experimenting with making changes (eg. to the diet), even if it is recommended in this book.
What about the internet and cell phone use?
According to recent studies, the average person spends 2 hours and 23 minutes per day on social media and 4 hours and 39 minutes daily on cell phones in general24. This is an enormous quantity of time to spend on devices and on social media in particular. Of note, solitary confinement (which is what cell phone use is) leads to a 31% increase in all-cause mortality in humans. There is a reason why this is the worst form of punishment we give to humans, and yet most of us voluntarily sign up for this for several hours a day.
Social media in general is the processed food of interaction. It is empty of substance, specifically designed to manipulate you to feel anxious, isolated, addicted, depressed and sick25. Most of the time you are not even interacting with a real person but rather a bot, an influencer presenting a fake existence, or a known person showing only a small, highly curated, slice of their life. It disrupts sleep and negatively influences lifestyle choices such as inactivity, fear of missing out (FOMO), and substance use. Furthermore, users are sedentary and isolated throughout the use, which are factors significantly associated with increased risk of death from all causes and particularly cardiovascular causes26.
Search and streaming video services are curated to keep you watching/using no matter what, manipulating your beliefs, biases, and validation. Note that when mammals are isolated, they are easily manipulated into addictive, negative and repetitive behavior. News organizations take advantage of this hourly, showing only the worst of society and further causing harm/bias.
The giant opportunity cost of losing interaction and activity in the real world, in addition to the above, makes social media and cell phone use in general an extensive risk factor that negatively impacts users' health and wellbeing on multiple levels. Social media, given the above, is no longer the “town square” where people can get reliable information (it's currently podcasts and individual blogs where accurate information comes from).
This line of technology has clearly made us weaker and less resilient/healthy. We recommend zero use of social media and news ingestion and a limited use of cell phones. While there may be positive aspects to social media use (like nicotine use is to mood), the negative aspects vastly outweigh the positive (like smoking is to cardiovascular health). Note we are not against technology per se, as many advances have helped people tremendously. As an example, we do advocate for smart watches which can perform calls and texts and have health benefits such as tracking, positive motivation etc. However, when that technology causes such clear and obvious harms, it must be abandoned with the same speed and completeness as it was initiated. See next paragraph for further detail.
What about religion, marriage, having kids, being in nature and other real-world interactions?
Across the board and among most studies, being religious, being married and having kids, being in a natural environment and having actual social interactions in the real world is associated with significant improvements in cardiovascular health and longevity outcomes. Religious practice leads to improved social support (a stable community), provides a sense of purpose higher than oneself, offers stress reduction (prayer and meditation), healthier lifestyle practices etc. In the Nurses’ Health Study, women who attended regular services had a 33% lower chance of death from cardiovascular causes27.
Marriage and having children in meta-analyses resulted in moderate reductions in all-cause mortality and survival from coronary artery disease and congestive heart failure (surprisingly more so in men than women)28. Single and separated/divorced males had the poorest outcomes in terms of cardiovascular disease mortality and morbidity of any subgroup. Essentially, having a purpose higher than yourself (regardless of said purpose, even a pet!) appears to be extremely beneficial from a cardiovascular standpoint.
The World Health Organization lists air pollution from cities as a substantial contributor to cardiovascular disease29. Additionally, being in nature has been shown to have positive effects on the prevention of ischemic cardiomyopathy, reductions in blood pressure, and improved outlook on life. To tie all of the above together, it has been known for decades that real social interactions and social support mitigates cardiovascular stressors, reducing the risk of addiction, anxiety/depression, hypertension and limiting ischemic and non-ischemic cardiovascular disease risk, all while providing a purpose in life by focusing on something bigger than ourselves. We recommend a minimum of 4 hours and 39 minutes without a cell phone anywhere near you during your downtime, and a daily minimum of 2 hours and 23 minutes in real face to face human social interaction, in addition to being in nature and seeing the sun regularly. This is human technology and it works really well.
Key Points: Social and Miscellaneous
There is a hierarchy of control to your life, start with the foundation and build up from there.
Find a higher purpose than yourself, which can be a religion, family, pet etc. From there, aim to build a foundation of exercise, then work on your diet and sleep. Once all of this is achieved, then it is time to consider supplements.
Cell phones and social media are the processed food of interaction, and end up making us sick socially, emotionally and ultimately physically. They isolate us, which is the worst form of punishment in our society, and yet we do it voluntarily (to the tune of several hours a day)!
Get out in nature and interact with people face to face regularly