Most of us have had cholesterol levels drawn where the different types of lipoproteins are explained as the bad LDL cholesterol, and the more protective good HDL. This idea came out of the Framingham Heart Study, a primary research project begun in 1948, that identified many risks for cardiovascular disease. But what if the good HDL cholesterol isn’t so good? High levels of low density lipoprotein (LDL) builds up in arterial walls and can cause atherosclerosis increasing ones risk of heart attacks and stroke. High density lipoprotein (HDL) on the other hand can lower overall cholesterol levels by binding with LDL and moving it to the liver, where it is excreted as waste. You can think of HDL as garbage trucks taking cholesterol away from the tissues, whereas LDL and other particles are delivery trucks of cholesterol. The more garbage trucks would mean less build up of cholesterol and fewer cardiovascular events. So a higher level of HDL is better…right?

Recent research reveals that very high HDL levels actually increase the risk of atherosclerotic cardiovascular disease (ASCVD). The authors defined high HDL as >80 mg/dL in men and >100 mg/dL in women. In a study of more than 400,000 people from the general population in the UK., men with HDL levels below 40 or above 80 and women with levels above 100 were at greater risk of both mortality from all causes and cardiovascular death in particular. Two smaller groups surprisingly with coronary disease and HDL levels over 80 had a 96% higher risk of dying overall than those with lower HDL levels.

There are some that are anti-inflammatory and others that can become pro-inflammatory if in an oxidative environment. So the HDL story is not so simple.

Data on HDL can vary on many levels. For example, there are ethnic variations, women have higher HDL levels than men and quitting smoking and moderate alcohol intake can increase HDL levels. Metabolic syndrome or pre-diabetes can lower HDL levels. Further, not all HDL particles are the same. There are some that are anti-inflammatory and others that can become pro-inflammatory if in an oxidative environment. So the HDL story is not so simple. Niacin, commonly used to treat elevated Lp(a) levels can significantly increase HDL levels but has been found to have no reductions in ASCVD. This suggests that there is a U-shaped curve for HDL cholesterol where very low levels are bad and very high levels are also bad. The best solution is the more Goldilocks than the Jekyll and Hyde result which is getting just the right amount of HDL lying between 40-80 mg/dL. But how do we identify how well the HDL family is working? In other words…we want more garbage trucks moving out the garbage (LDL) but we don’t want the garbage trucks stuck in traffic.

One solution would be to measure cholesterol efflux. This was done in the Dallas Heart Study, which was a better predictor of cardiovascular (CV) risk. If you have low cholesterol efflux, then you are at risk. A high efflux means you are good. This marker takes the guess work out of whether high HDL particles are effective and you don’t have to deal with all the different sub-particles in the HDL family.

Unfortunately, we cannot measure cholesterol efflux easily, so the next best thing is to treat what we can control which is high LDL and low HDL. You may have more efficient trucks but not enough of them. People need to know that high HDL is not a universal protective factor for atherosclerosis and puts them actually at higher risk. So lowering LDL through healthy lifestyle changes such as exercise, and a high fiber, low sugar diet is very effective.  Estrogen has been shown to be protective for women starting in early menopause. And especially avoid smoking which can raise LDL and lower HDL.

References: Denworth, L. When “Good” Cholesterol Turns Bad. ScientificAmerican.com. The Science of Health.  June 2023.

Lin, P. Are higher HDL-C levels really better? Obesity, Metabolic Syndrome, and Prediabetes. Protective Effect of HDL-C Against Cardiovascular Disease. August 01, 2023.

Long haul COVID, otherwise known as SARS-CoV-2 is still with us and growing. Its defined as prolonged recovery lasting more than 3 months after first contracting the virus. It now effects 65 million people around the world, about 1 in 13 adults in the U.S. We didn’t know what to make of this virus when it first appeared.  Then it became clear that following recovery from COVID-19, some patients were left with persistent  symptoms similar to other conditions such as Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Long-haul COVID and Chronic Fatigue Syndrome have a lot in common.

The research behind ME/CFS did not emerge until the 1980’s. The underlying biological abnormalities were uncertain and standard clinical laboratory tests were normal. Skeptics felt patients were suffering from depression or fabricating their symptoms to achieve some secondary gain. It wasn’t until 2020 that thousands of published scientific papers had identified multiple abnormalities and research on the illness was underway at laboratories around the world. Sound familiar??

Not only do ME/CFS and long-haul COVID share symptoms, but they have similar underlying biological abnormalities.

Many people including physicians still don’t believe that long-haul COVID exists. Ignoring this condition that has disrupted so many people’s lives only delays further research desperately needed for  treatment.  Long-haul COVID and Chronic Fatigue Syndrome have a lot in common such as brain fog, executive function loss, inability to drive, post-exertion malaise, disrupted sleep, orthostatic intolerance, joint and muscle pain, racing heart rate and gastrointestinal symptoms. Not only do ME/CFS and long-haul COVID share symptoms, but they have similar underlying biological abnormalities. Here are some of the most recent findings that are noted in both illnesses:

Neurological: Cognitive deficits, especially in reaction and attention time. Reduced cerebral blood flow, white matter abnormalities on MRI, reduced sleep efficiency, down-regulation of the hypothalamic-pituitary-adrenal axis and autonomic dysfunction (POTS).

Immunological and Infectious: Both illnesses involve elevated levels of cytokines, particularly pro-inflammatory cytokines, high levels of autoantibodies, including antibodies that target the nervous system. Reactivation of latent herpes viruses, particularly Epstein Barr virus (EBV) commonly know as “Mono”, human herpes virus-6 and cytomegalovirus, and a pro-inflammatory gut microbiome.

Metabolic: Reduced ability to generate ATP energy from glucose, fatty acids and amino acids. Increased oxidative stress. Increased rates of insulin resistance and type 2 diabetes, early onset dementia and autoimmune diseases. Both conditions increase oxidative stress.

Cardiovascular/Cardiopulmonary: exercise capacity is diminished, ventilatory efficiency is reduced and endothelial dysfunction occurs. Platelets are hyperactivated forming micro-clots.

Research is finding that after recovery from acute infections of ME/CFS and Long-haul COVID, some patients will have persistent symptoms of a variety of viral, bacterial, and protozoan agents, including EBV, West Nile virus, Borrelia burgdorferi (Lyme disease co-infection) and Giardia lamblia. A similar syndrome of persisting symptoms has been reported following “recover” from major physical trauma, sometimes called “SICU” syndrome.

So why would multiple different infectious agents and major physical trauma produce a similar syndrome? One hypothesis is that this syndrome is driven by an evolutionary protective response in which it changes an animals behavior. The symptoms of fatigue and brain fog discourage activities that consume energy (ATP) like movement, thinking and digesting. This frees up available supplies of energy for the fight against infections or injury. In some people, perhaps this protective response is not turned off when the infections are resolved and the injury is healed, or some on-going inflammation in the body continually signals the brain that the battle is still not over.

The National Institute of Health (NIH) has invested more than $1 billion to understand the biology of long-haul COVID. This investment will hopefully also provide answers for people suffering from ME/CFS as well as other similar chronic conditions. For now the best treatment has been integrative medicine. This type of medicine has addressed post viral conditions for decades. The use of herbal medicine, acupuncture, nutritional infusions and individualized assessment and treatments have been very successful in recovery and long-term resilience. Go to Coloradocovidcare.com for more information CCC

Komaroff, A., Lipkin, W. ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature. Front medicine 2023; 10:1187163

Davis, H, McCorkell, L, Vogel, J, Topol, E. Long COVID: major findings, mechanisms  and recommendations. Nat Rev Microbiol 2023.

 

 

 

An estimated 30% of major depressive disorders are resistant to treatment in the United States. This means a person has tried at least 2 antidepressants for at last 6 weeks each and has not experienced remission or at least a 50% improvement in mood. Two common treatments for this condition are Ketamine or Electroconvulsive therapy for resistant depression. Ketamine has drawn a lot of attention recently. This drug has been studied and administered in controlled, clinical settings to help with treatment-resistant depression and other conditions. Ketamine is an anesthetic and a sedative and has been used to treat suicidal thoughts. . It causes a dissociative experience that makes the brain more malleable and receptive to therapy or alternative ways of thinking. Ketamine influences the neurotransmitter, Glutamate while its causes a cascade of biologic, structural and functional changes in the brain.

Electroconvulsive therapy (ECT) is a medical treatment also used for drug-resistant depression and bipolar disorder. It involves a brief electrical stimulation of the brain to create a generalized cerebral seizure while the person is under anesthesia. Dopamine function is thought to be impaired in people with depression causing impairment in concentration, motivation and pleasure. ECT improves this system while lowering stress hormones and helps feedback regulation.

While both of these treatments have rapid responses (hours to days), is there one better than the other? A meta-analysis was done in which researchers examined 6 studies looking at Ketamine infusions (3 times per week for 2 weeks) and ECT (3 times/week for 4 weeks). Results showed that at 1 month, ECT was significantly more effective than ketamine, with remission rates of 63% versus 43% in the largest study. Both Ketamine and ECT were effective in reducing suicidal ideation. ECT had more cognitive side effects and ketamine was associated with more depersonalization, vertigo and visual disturbance. The effects of both treatments waned over time with comparable outcomes at 3 and 12 months.

There is evidence of long-term maintenance with ECT. Unfortunately, intravenous Ketamine is not reimbursed by insurance companies which is the most bioavailable, precise treatment. Ketamine comes in different forms such as oral, topical, intramuscular, sublingual and intranasal. In the U.S the only FDA-approved form is nasal esketamine (Spravato) but it is only 25-50% bioavailable. Bioavailability means the amount of medication that actually goes to the bodies tissues and the brain. Intravenous treatments are 100% bioavailable. When you take other forms of the drug, parts of the active ingredients don’t go to the bloodstream, but get digested and altered into an unusable form, metabolized and excreted into your body. Although ECT appears to be superior, ketamine might be preferred by those looking for more rapid effects and wanting to avoid ECT’s short-term cognitive effects.

Youth depression rates have risen from 12.9% to 25.2% from pre-pandemic to 2021.

Mental health illness has risen in the United States, with about 20% of people in the country experiencing some form of it. There are many reasons for this sharp increase. The increase can be due to social media, the COVID-19 pandemic, and societal trends resulting in smaller family units, increased financial pressure, social isolation and political and economic stressors. Youth depression rates have risen from 12.9% to 25.2% from pre-pandemic to 2021. More than 50 million Americans struggle with mental illness and most lack access to adequate mental health treatment.

Other brain stimulation treatments include Transcranial magnetic stimulation (TMS) and Vagus nerve stimulation (VNS). Unlike ECT, TMS does not cause a seizure and the patient stays awake through the entire non-invasive process. Rapidly alternating magnetic fields stimulate specific areas of the brain. It is usually administered 4 or 5 times per week for 4-6 weeks. Side effects are usually mild including headaches, twitching and pain at the stimulation site.

Vagus nerve stimulation was originally used to treat seizures but can be effective in treating depression that has not responded to other therapies. It involves implanting an electrical pulse generator under the skin in the patient’s chest that provides intermittent electrical stimulation to the vagus nerve in the neck. Response may take months, so it is not used as a treatment for acute severe depression.

Mental health is so important for our overall health because of its relationship with our physical health. For example, depression raises the risk of diabetes, heart disease and stroke. Similarly, the presence of chronic illnesses can increase the risk of mental illness. Solutions consist of spending time in nature, healthy eating and exercise, connecting with others, reducing stress and getting enough sleep. Other effective treatments include psychotherapy, and many of the above medications or procedures.

Reference: dosomething.org. “11 Facts About Mental Health”. 2023.

Zimmerman, R. Ketamine for depression: What it feels like and who it can help. The Washington Post. 9/12/2022.

The American Psychiatric Association. What is Electroconvulsive therapy? Psychiatry.org

Principium Psychiatry. IV vs Oral Intramuscular vs Intranasal Ketamine: Why route matters. principiumpsychiatry.com

Rhee TG et al. Efficacy and safety of ketamine vs electroconvulsive therapy among patients with major depressive episode: A systemic review and meta-analysis. JAMA Psychiatry 2022. Oct 19; [e-pub]. (https://doi.org/10.1001/jamapsychiatr. 2022.3352)

Brain Therapy TMS: Transcranial magnetic Stimulation. Top 5 treatment-resistant depression statistics you need to know. May 28, 2021.

We have heard the term “probiotics” which refers to the live bacteria and yeast that help maintain or improve the healthy microflora in the gut. We may also be familiar with “prebiotics” which are the fermented foods that FEED these amazing bacteria, as well as viruses and yeast species. But postbiotics are also part of the gut-brain axis that needs to be discussed. All three of these types of “biotics” (from the Greek “bios” meaning “for life”) should be part of the discussion when it comes to our gut, which is the largest organ in the body that holds 70% of our immune system. So it needs to be happy, healthy and well cared for.

So what are “postbiotics’? They are defined as the nonviable bacterial or metabolic products from microorganisms that have biological activity in the host. It is basically the waste left behind by the digestion of pre and probiotics. Some postbiotics from non-viable microorganisms come from Lactobacillus species.  These precision probiotics are strains that have precise effects in the body and brain. For instance, there is growing evidence of antidepressant effects of GABA secreted by Lacticaseibacillus rhamnosus and Lacticaseibacillus casei that travels through the nervous system and crosses the blood-brain-barrier altering the expression of GABA receptors that may lead to a reduction in depression. Another GABA secreting bacteria, Levilactobacillus brevis may help with sleep as well as reducing depression.

The fact is that we make more neurotransmitters in our gut than the brain. Certain bacteria can send serotonin, GABA, dopamine and norepinephrine to the brain. Postbiotics are especially helpful in people who are sensitive to probiotics, because they are less likely to cause gas and bloating. It also helps those whom are  immune compromised as they pose no risk for infection.

As I mentioned before, postbiotics can include inactivated probiotics or cell wall fragments. This includes metabolites such as short chain fatty acids (SCFA), vitamins (folate, B12, Vitamin K), enzymes and bacterial lysates and more. The most common postbiotics from nonviable organisms come from lactobacillus species, Bifidobacterium species and Saccharomyces (yeast) and bacillus species. The SCFA’s, primarily sodium butyrate are fuel for the microbiota and help regulate GI function, blood pressure and act as intermediaries between the gut and the brain.

Postbiotics have many functions: they strengthen the tight junctions in the gut, improve leaky gut, help with immune modulation, protect from infection and mitigating allergies.

They also help support healthy metabolism by lowering the risk of insulin resistance and the regulation of hemoglobin A1c (blood sugar levels). More and more human studies are being conducted and have observed improvements in irritable bowel syndrome symptoms, immune support (reducing risk of upper respiratory infections and less allergic symptoms), and metabolic support by lowering systolic blood pressure and decreasing elevated liver enzymes as well as total cholesterol and LDL.

Postbiotics are an important addition to gut-brain therapeutics. More research is needed but the existing studies show that dosing  varies according to the specific postbiotic and the conditions being used to treat. They are effective in supporting the gut and building foundational health from the gut up.

References: Fidler, M. “Postbiotics: The newest addition to gut-brain therapeutics”. Element by Emerson Ecologics. Issue #6 p. 30-33. 2022.

Lowry, C.  “Understanding the Gut Brain: Stress, Appetite, Digestion and Mood”. Conference in Lafayette CO. 3/13/2023.

Golen, T. “What are Postbiotics?” Harvard Health Publishing: Harvard Medical School.  Nov. 1 2021.