Alzheimer’s disease and dementia prevalence and deaths are on the rise, claiming over 6,000 lives in the USA every week! Yet many people don’t even know their APOE genotype, which arguably has the biggest impact on future Alzheimer’s disease and dementia as well as cardiovascular disease risk.

In this show we dive deeper into what the APOE gene does and how knowing this info can help tweak your nutrition and lifestyle helping to reduce risk of future disease—especially if you have one or two copies of the APOE ε4 gene.

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Time Stamps:

0:00 Intro
00:53 APOE is a gene that makes proteins that are involved in lipid binding.
01:10 APOE and Immunity
01:39 APOE 4 alleles and Alzheimer’s disease risk
03:13 3 different APOE isoforms: APOE2, APOE3, APOE4 allele.
03:44 Having the gene does not mean that you will get the disease.
04:35 APOE is involved in lipid metabolism
05:30 Lipoproteins and lipids transport
06:05 APOE can redistribute lipids across tissues and cell types.
07:40 APOE is secreted by the liver with VLDL and bile acids
08:00 Lipoprotein lipase facilitates your metabolic deposits. Hormone sensitive lipase facilitates your metabolic withdrawals.
09:42 Your omega 3 index and APE 4 isoform.
11:35 APOE4 and cholesterol
11:45 ApoB VS ApoE
12:09 APOE2 carriers tend to have a less atherogenic lipid profile.
12:15 APOE4 carriers are associated with decreased levels of APOE triglycerides and increased levels of APOB in lipoproteins
13:12 APOE4 puts genotype carriers at increased risk for heart disease. This is likely due to the association with APOE4 and elevated LDL and Apolipoprotein B.
14:07 APOE4 primes your microglia to be more inflammatory. Microglia are brain immune cells. They are involved in synaptic processing, pruning of cells, shaping neurons, and removing inflammatory debris. APOE4 carriers have decreased cerebral glucose metabolism and increased levels of beta amyloid and tau protein.
15:50 With APOE4, there are changes and increase of tau protein within the neurons. There are also alterations in the blood brain barrier integrity.
16:00 To preserve the integrity of the brain, moderate alcohol consumption, increase exercise, incorporate sauna therapy and sauna bathing, as it effects cerebral blood flow.
16:45 APOE is expressed in astrocytes, microglia and other vascular cells within the brain. Blood brain barrier prevents toxins and metabolic waste from going into your brain. Increased expression of APOE is detected in stressed neurons.
17:42 APOE isoforms affect lipid transport, glucose metabolism, mitochondrial function, synaptic plasticity, beta amyloid protein expression, tau protein and cerebral vascular function within the brain.
18:18 Ratio of APOE4 allele correlates with loss of gray matter volume and abnormal glucose metabolism, a hallmark of Alzheimer’s and dementia.
19:00 APOE4 is the greatest genetic risk factor for late onset Alzheimer’s disease. It also influences the risk and outcomes for stroke, MS, Parkinson’s disease, and frontotemporal dementia.
22:11 A low carb diet, high in wild caught fish, is protective for APOE4 carriers. It impacts brain metabolism and lipid levels favorably. Drive your glycemic load down.
24:05 If you are over the age of 50 and have one or two copies of the APOE4 allele, consider microdosing with rapamycin. Rapamycin is an mTOR inhibitor. It may delay the onset of Alzheimer’s and dementia.

Overeating, especially at night, can lead to fat and weight gain. We review some practical tips to help prevent the over-consumption of food and special considerations during the holiday season.

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Standard lipid panels are actually mathematical approximations. Emerging data suggests using the very affordable ApoB to ApoA1 ratio more accurately assess cardiometabolic disease risk.

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Time Stamps

0:45 ApoB why it’s more accurate

1:30 High LDL on a ketogenic diet

2:24 Heart disease deaths increase in the winter

2:59 High LDL after fasted exercise

4:50 What ApoB means and why it matters

7:15 Why Omega-6 seed oils are bad if your LDL is high

9:11 Request your ApoB to A1 ratio instead

9:38 Standard cholesterol tests are a mathematical estimate

12:06: HDL and ApoA-1, how it’s cardioprotective

12:45 Harvard case study of LDL increases on a Keto diet

19:25 Advanced lipoprotein particle testing overview

Assuming you've recently ordered the expanded labs that we suggested on page one of the Blood Work Cheat Sheet, here's a additional assessments to consider to see if your lifestyle is maximizing your health.

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Time Stamps

00:25 Measuring your omega 3 index is more important for men and post-menopausal women. Hormone changes in post-menopausal women greatly increases risk of heart disease.
0:44 Bill Harris, PhD explains the omega-3 index
2:23 An omega 3 index below 4%, reflects higher risk of sudden cardiac death, having a fatal heart attack, should they have a heart attack.
03:40 Omega 3s in the 6% to 8% range is optimal for reducing risk of sudden cardiac death, compared to those of us with omega 3 index of 3 or 4%.
04:00 OmegaQuant offers an at home test of your Omega 3s. The OmegaQuant test quantifies the percentage of EPA and DHA in your red blood cell membranes. They also look at palmitate.
04:15 When palmitate increases, it is a proxy that potentially de novo lipogenesis is occurring. This means that insulin is causing your liver to increase fatty acid synthesis, which can result in insulin resistance and fat gain.
05:15 A DEXA scan will show you where your fat is being distributed. It will also give insights into your bone mineral density. Ageing and gaining fat around the middle, has been linked with low mineral density and muscle mass.
05:23 Osteosarcopenic obesity is the simultaneous loss of bone mineral density, loss of muscle and gain of fat.
03:50 A DEXA scan every 2 years tracks the trajectory of your body composition and your muscle. The amount of fat on your body is a reflection of your vitality.
05:25 A full body MRI every 5 years or so can be done if you have cancer in your close family or you are a former smoker.
06:42 If cardiovascular disease runs in your family, or you have sleep apnea, iron overload or insulin resistance, you may consider testing your CIMT (carotid intimal thickness). It shows how much atherosclerosis or stenosis is in the carotid arteries. A coronary artery calcium score is more invasive.
07:30 The arterial pulse wave velocity test is non-invasive. It measures the elasticity of your vessels. Stiff arteries are characteristic of inflammation.

Let's review some of the most resent Excess Death figures for 2021 and compare and contrast states like Florida to California and more. We also discuss on the first in vitro studies finding new mechanistic evidence that Omicron is indeed more mild than previous variants.

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Time Stamps:

0:20 New hints omicron will be mild
6:19 Excess Deaths
9:40 California VS Florida
11:08: Indirect effects of social isolation, being sedentary and more
17:28 Consequences of lockdowns and isolation
19:13 Recidivism in weight gain

Exercise is arguably one of the fastest ways to decrease blood sugar and insulin as well as prime the body to burn more fat. We review a recent paper that discusses the history and new research about exercise as a glucose and insulin lowering tool.

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Time Stamps:

0:00 Intro
0:05 Insulin resistance is the root cause of many of today’s premature deaths and chronic disease expression.
0:32 Moving/exercising, especially in the post meal window, makes changes that decrease glucose levels and make your skeletal muscle more sensitive to the effects of insulin. This leads to reduced insulin output by your pancreas.
1:40 Insulin is involved in post meal processing and anabolic reaction. It helps build. It helps replenish depleted glycogen. It helps, in the post exercise window, to increase amino acid biosynthesis.
1:58 Exercise is favorable, but it is catabolic, meaning that it tears down.
2:23 Post meal glycemic levels flatten with exercise. Diabetics tend to use less insulin on days when they exercise and blood sugar levels decrease more quickly.
4:48 During exercise your muscles become a glucose sponge; muscle glucose uptake increases in an intensity and duration dependent manner. Glucose is needed to make ATP in your muscles.
5:40 Exercise increases the expression and sensitivity of GLUT4 transporter. GLUT4 can be desensitized by persistent elevation of glucose levels.
9:35 Insulin is a potent inhibitor of adipose tissue lipolysis, the ability of your fat cells to release stored lipids.
10:10 Pre-workout or intra-workout carbohydrates may slow down your fat lipolysis, or fat burning. If fat loss is your goal, you may want to consider exercising in a fasted state.
11:30 When you exercise, your adrenal glands release adrenaline and noradrenaline. These enhance the liberation of stored fat from your fat cells to use for cellular energy when you exercise.
11:50 Fasting and exercise both elevate adrenals. Prolonged fasting and overexercising can be hard on your adrenals.
12:40 High insulin reduces the normally a progressive rise in free fatty acid oxidation during exercise.
13:15 One Legged Study: The exercised leg increased its muscle glycogen stores to levels twice that of the sedentary leg. Exercise increases the ability of your moving muscles to store glycogen.
13:50 When you move your muscles, you are depleting glycogen with the muscle. Exercise helps your muscles become more insulin sensitive by depleting glycogen within the muscle, causing muscles to be more insulin sensitive in the post exercise window. A glycogen-depleting workout is a good way to kickoff your fast.
15:25 After dinner starts your overnight fast. Perhaps you could take a brisk walk or lift weights before dinner to blunt the post meal glycemic index level.
15:50 Doing your post meal exercise when your post meal blood glucose level peaks, has the best ability to reduce glucose levels. This peak is most often 45 to 60 minutes after a meal.
16:23 Eat early. Sleep early. Eat your carbs commensurate with your physical activity level. Go for a walk after your meal.
17:15 Insulin sensitivity can be boosted for up to 48 hours after a single exercise session. Exercise increases the transport of glucose from the bloodstream into muscles by a factor of 34.
18:45 Eccentric exercise, slow descent, muscle damaging effects can cause a transient reduction in insulin sensitivity. Moderation is key.
19:40 You are most insulin sensitive in the morning. You become more insulin resistant as the day progresses. Exercise when you can. Afternoon resistance training can blunt your dinner glycemic index.
20:45 Sprinkle exercise throughout the day. Researchers call them exercise snacks. These snacks can be as simple as going for walks.
21:45 Big surges glycemic variability/glycemic levels are a big problem.

Researchers at Stanford just published two of the most fascinating studies to date linking overweight/obesity with higher risk for severe COVID.

These related but different studies both find COVID (SARS-CoV-2) directly infects fat cells (concentrating virus) and cranking blood sugar and inflammatory processes. The findings have important public health implications if we're serious about saving lives. 

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Time Stamps:

0:00 Intro
2:32 InfectObesity 101
2:48 Study #1 Virus infects fat cells
4:22 Belly Fat is a problem
5:32 Infected fat cells trigger inflammation
6:20 Fat Cells altered in children
7:17 Endothelial Dysfunction and erectile dysfunction
7:52 Fat cells contain high levels of virus
11:04 Fat cell infection skews blood sugar
11:44 Omega-3 Index
14:01 Hyperglycemia from fat cell dysfunction
15:58 Fitness should be mandated
18:00 Key takeaways from study #2
20:00 Skewed leptin/adiponectin suggest fat cell is the problem
21:00 Restoring fat cell dysfunction

Let's discuss the potential good news with regards to the recent variant of concern and how these mutations can lead to reduced severity of illness that's easier to catch.

We discuss the ACE2 receptor density in the upper VS lower airway and more.

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Time Stamps

0:45 Transmission VS Virulence Trade off
1:30 New mutations, what they mean
3:42 Location of ACE2: why it matters
4:31 Most important point of this paper
5:53 Testing Vitamin D at home
6:23 Details of the new mutations and ACE2
7:42 Upper airway infections are easier to transmit, catch
8:14 The transmission VS virulence trade off
9:52 ACE2 receptors have gradient densities in the airway
10:50 I could be wrong!

A large body of research suggests vitamin D impacts sleep quality and sleep duration as well as neurotransmitter levels in the brain. Here's an overview of the latest science--which is timely if you live in norther latitudes.

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Episode Time Stamps:

0:00 Intro
1:37 Vitamin D and Sleep
2:07 Dr. Stasha Gominak, MD Vitamin D and Sleep Podcast
2:16 Vitamin D and Gut Health
2:31 Vitamin D Metabolism Basics 
4:56 Factors that impact vitamin D levels
5:54 Optimal Vitamin D levels
6:42 Classical VS Non-Classical pathways linked with Vitamin D 
8:05 Vitamin D and sleep details
8:31 Vitamin D and sleep disordered breathing
9:05 Vitamin and sleep details
10:16 Vitamin D and Circadian Rhythms
11:00 Dosing Vitamin D at night
12:38 Vitamin D and Brain Development
13:45 Vitamin D is very important for children
14:57 Big picture re: Vitamin D and sleep
15:47 Vitamin D Blood spot test
16:13 Optimal Vitamin D levels this winter
16:50 Dosing Vitamin D prior to bed
17:52 Vitamin K and Vitamin D

With all the buzz around boosters, family friends used data to help guide their family’s decision making process by testing their antibody levels and T cell immunity. We review their recent labs and discuss how data can and should be used to help you make health related decisions.

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Links to interview with ZDoggMD: https://youtu.be/H3pAD0LOkZg

Time Stamps: 

2:00 Booster hysteria: Is based on science

3:00 How much added benefit do boosters offer

6:00 Using data, not emotion, to drive policy

11:00 Reviewing families antibodies

14:10 Monica Gandhi MD, MPH on T cell VS B Cell Immunity

16:00 Reviewing antibodies and T Cells

20:00 Conclusion: using data to drive decisions

Your body composition changes as you age, especially after menopause for women. Compressed feeding patterns like intermittent fasting (IF & TRF) can help improve metabolic health and prevent fat gain throughout lifespan. Deanna Mutzel joins us to discuss how she uses Intermittent Fasting and OMAD as a tool on busy days.

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Connect with Deanna: http://deannamutzel.com

Time Stamps

0:00 Intro
0:17 Fasting as a tool when life gets busy
1:34 Fasting can help with energy, mental clarity
3:15 Considering energy balance over a longer period of time
3:45 Undulating your calories
4:45 Vitamin D should be considered seasonally
6:39 Find out how snacking weak-spots
10:39 Getting the whole family on board
9:10 Using exercise to buffer glucose surges
12:01 Making your own chips
15:15 Walking "snacks" throughout the day
18:40 Changing your identity is important for success
19:49 Making exercise easier
21:47 Cold showers in the winter
24:00 Easing into fasting
25:30 Plant based diets and health
30:00 Changing your feeding window with the seasons