A Year of Legends: Best of 2024 at Dr. Kara Fitzgerald
Did you know that the Younger You program targets more than aging alone? That’s in part because most non-communicable diseases are actually intricately tied into the epigenetic aging phenomenon – in fact, biological aging is the biggest risk factor for chronic disease. In this blog, we’ll take a look at how optimizing DNA methylation (through nutrition and lifestyle, as we do in Younger You), may positively impact several common health conditions.
1. Obesity
The truth is that weight—as measured by BMI—is associated with accelerated aging, as measured by DNA methylation.
Based on what we saw in our research study with a few participants (most didn’t need to lose weight as they were healthy at the start) and in our clinical practice, those who follow the Younger You Intensive, certainly, and even the Younger You Everyday, and who can benefit from weight loss do lose weight. In fact, even the healthy cohort that we studied still lost an average of 4.61 lbs on the program.
The Younger You Intensive employs the well-established weight-loss guidelines of being a low-glycemic, keto-leaning program that incorporates mild time-restricted eating (otherwise known as intermittent fasting). It’s also free of allergenic foods, such as dairy and gluten, so it’s also anti-inflammatory. Taken altogether, the Younger You Intensive lowers inflammation and increases energy and satiety, which allows for weight loss, if needed.
Following the Younger You principles of avoiding toxins also reduces your exposure to endocrine-disrupting chemicals, also known as obesogens, that can contribute to the hormonal and epigenetic dysregulation that is associated with metabolic impairment and weight gain.
On top of these direct influences on weight loss (and this doesn’t even include the weight-loss benefits of regular moderate exercise, improved sleep, and boosted relaxation), modulating your DNA methylation may also affect expression of obesity-associated genes that influence what your body does with calories. If these genes are shut off due to hypermethylation, you’re more than twice as likely to be obese. Because the Younger You program includes ample amounts of foods that affect the methylation-demethylation balance, the eating plan may help turn back on the genes that promote a healthy weight.
By the same mechanism, eating the DNA methylation–supportive nutrients that are a hallmark of the Younger You program may help to change the epigenetic patterns that you’ve inherited from parents, grandparents, and great-grandparents. No more “thrifty gene” metabolism!
2. Alzheimer’s Disease
While there can be a genetic component to Alzheimer’s disease, 95 percent of those who have it have the nongenetic form. As with obesity, it’s known that epigenetic mechanisms play a variety of crucial roles in the development of Alzheimer’s disease, to the extent that several epigenetic-based therapies are being considered now.
Most broadly, accelerated biological age is associated with Alzheimer’s, and patients with Alzheimer’s are biologically older than same-aged healthy folks. Alzheimer’s and other neurodegenerative diseases are accompanied by marked global methylation decrease overall (very often this population has elevated homocysteine, a marker of decreased methylation), along with a higher expression of genes you don’t want to be turned on and a lower expression of genes you do want in the on position.
More specifically, a number of genes involved in Alzheimer’s disease have been found to have aberrant methylation patterns in those with the disease as compared to those without the disease, meaning some genes are on when they should be off, or off when they should be on.
The APP (amyloid precursor protein) gene gives rise to amyloid beta protein when it is in the on position, and APP is often in abundance in the brains of Alzheimer’s patients. When we’re young, this gene tends toward the off position; as we age, it can turn on, which likely plays a role in higher levels of beta amyloid in the brain and, thus, higher risk of Alzheimer’s disease. Furthermore, the gene for the protein that breaks down beta amyloid is actually hypermethylated and turned off—a double Alzheimer’s whammy. In addition, the ApoE4 gene, well known to be associated with the disease, has a complex and unusual pattern of methylation, with some areas hypomethylated and others hypermethylated. Scientists speculate that these changes may induce the pathologic alterations seen in the brains of Alzheimer’s patients.
From my standpoint, any program effectively addressing Alzheimer’s disease requires interventions that address DNA methylation and epigenetics in general, supporting both methylation and demethylation.
The functional medicine approach to Alzheimer’s disease (as developed by Dale Bredesen, MD) is a powerful intervention for both preventing and treating Alzheimer’s disease—a 2022 multicenter clinical trial validated its benefit. Much of the Younger You program and the Bredesen program overlap: Each focuses on healthy, low-carb/keto-leaning, good-fat and polyphenol-rich foods with time-restricted eating windows. Each prioritizes exercise, sleep, and stress reduction. And each approach minimizes toxin exposures, which is essential in protecting brain function and DNA methylation. Dr. Bredesen also recognizes hypomethylation as an issue and pays attention to homocysteine levels in his patients.
Where Younger You differs from Bredesen’s approach is its targeted focus on balancing DNA methylation.
In our clinic, we use the Bredesen approach as a foundation for our patients with neurodegenerative conditions and then layer Younger You components onto his program. Our patients routinely experience lower levels of inflammation, homocysteine, and toxins and demonstrate improved nutrient status. We see the best outcomes in cognitive scores with mild cognitive impairment (MCI), although we can see favorable changes in cognition even in those with advanced disease.
Reducing elevated levels of homocysteine, the biomarker associated with poor overall methylation, including DNA methylation, has also been shown to slow the rate of whole brain atrophy and cognitive decline in elderly people with cognitive impairment. And the patients in our clinic routinely lower their homocysteine to healthy levels when following the Younger You program.
3. Cardiovascular Disease
Cardiovascular disease is the number one cause of death worldwide. We cannot overstate the significance of heart disease in terms of quality of life and medical costs: it’s absolutely enormous.
Bio age, as measured by DNA methylation patterns, is well correlated with risk of cardiovascular disease—the higher your bio or chronological age, the greater your risk of heart disease.
In addition, inherited altered DNA methylation patterns—like those seen in the Dutch Hunger Winter and Överkalix studies—contribute to conditions including diabetes, hypertension, and obesity that increase your cardiovascular risk.
Disordered methylation patterns on numerous genes associated with hypertension, atherosclerosis, heart failure, and myocardial infarction have been identified in humans. What I find most interesting is the connection between early and midlife stress and altered DNA methylation patterns that have been associated with later onset heart disease and cognitive decline. Of particular note is the gene NR3C1, which codes for the human glucocorticoid receptor (glucocorticoid is a class of steroid hormone that is released during stressful times and plays many roles, including curbing inflammation). Different methylation patterns of NR3C1 have been identified in a broad spectrum of stress disorders, heart disease, and cognitive decline, making it a common gene of interest in all of these conditions.
Elevated homocysteine, a foundational marker of imbalanced total methylation (including DNA methylation), has long been touted as a risk factor for cardiovascular disease and stroke. Yet, the research does not clearly show that simply lowering homocysteine alone will prevent heart disease.
So how do we interpret these seemingly conflicting findings? DNA methylation patterns, changed by broad environmental exposures ranging from previous generational experience to early and midlife stress exposures, to diet, toxins, exercise patterns, and more all influence methylation patterns that in turn influence heart disease risk. A singular focus on correcting homocysteine—or limiting treatment to cardiology alone—isn’t enough; as with the other conditions in this article, a full Younger You Intensive may favorably influence the occurrence of heart disease in a broad, beneficial manner, as getting biologically younger reduces risk.
4. Type 2 Diabetes
In the United States alone, a diabetic is newly diagnosed every twenty seconds. This metabolic disease burns through bio age like dry kindling on a hot day: diabetes is associated with a six- to nine-year increase in biological age!
It’s well established that type 2 diabetes results in “general dysregulation of DNA methylation” with far-reaching effects, including hypermethylation of important tumor-suppressor genes and antioxidant-regulating genes, as well as a particular gene that impacts insulin, PPARGC1A.
The obesogenic toxins that play a role in excess weight—like PCBs and pesticides—even in low doses of exposure, are also potent drivers of diabetes, in part because they contribute to abnormal DNA methylation patterns. And higher levels of exposure to obesogens are associated with a whopping thirty-eight-plus-fold increase in diabetes!
The good news is that type 2 diabetes is very responsive to the Younger You protocol.
5. Depression
Mental health has epigenetic roots. In adults with depression, two key genes have been found to be hypermethylated and inhibited:
- Brain-derived neurotrophic factor (BDNF), which is involved in the formation of new neurons and is vital to learning, memory, higher thinking, and mood, is often hypermethylated and switched off. In early life, adverse chemical toxin exposures can negatively impact DNA methylation and stressful events can become biologically embedded in the epigenome, changing BDNF gene methylation, which has potential long-lasting impact on behavior and memory. Exercise, a fundamental part of both the Intensive and Everyday programs, helps BDNF re-expression.
- Depression, along with alcoholism and obsessive-compulsive disorder, is associated with specific epigenetic changes to the serotonin transporter gene (SLC6A4), which is involved in serotonin reuptake. Interestingly, SLC64A is also involved in energy metabolism and its methylation status can predict obesity over the life span.
In addition to these two genes, the gene for receptors of oxytocin—known as the “love hormone”— also plays a role in depression. When the gene is hypermethylated and turned off, it lowers empathy and prompts a lack of connection to others, both common experiences that can happen with depression. One study on depression in African American women involved one hundred middle-aged participants. It found that when the oxytocin receptors were hypermethylated and off, the women were more likely to have negative thinking patterns, such as pessimism and distrust, both common in depression—and this effect was seen regardless of relationship status, childhood trauma, age, and overall methylation status. The researchers concluded: “epigenetic regulation of the oxytocin system may be a mechanism whereby the negative cognitions central to depression are biologically embedded.” In other words, getting stuck in a negative thinking loop may further embed the experience you’re thinking about in your epigenome.
In our clinic, we’ve seen time and time again that the combination of a diet rich in DNA methylation–supportive nutrients as well as moderate exercise, meditation, and sleep all support mood and mental health.
6. Autoimmune Diseases and Allergies
Both autoimmune diseases and allergies are hallmarks of an overreactive immune system: in autoimmunity, your immune system goes on the attack of your own tissues; in allergy, it mounts an overwhelming immune response to a benign substance. Incidence of both is markedly on the rise across the globe, which means that genetics, while there is a connection, doesn’t explain the increase. That leaves epigenetics.
While clear, actionable epigenetic patterns in autoimmunity and allergy are still being established, what we know so far is that epigenetic deregulation of the immune system contributes to disease onset and severity—meaning the imbalance begins long before symptoms manifest. As a specific example, the DNA methylation of genes in key insulin-producing cells is considered “potentially causal” for autoimmune type 1 diabetes and may be present years before the onset of diabetes. The other thing we currently know about these conditions is that lower methylation reduces immune control, allowing proinflammatory genes to be hypomethylated and turned on, something we see in other chronic diseases and in aging itself.
A 2021 study (that cited our study!) showed that women with the autoimmune disease lupus (SLE) had higher rates of hypomethylation on a specific immune cell gene when disease activity was high, and those who ate a higher methyl donor diet reported significantly lower disease activity. The authors concluded that “dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.”
It’s been known for decades that autoimmune and allergic diseases share underlying root causes, including genetic and epigenetic susceptibility, filtered through poor diet, imbalanced microbiome, leaky gut, hormone imbalances, toxin exposures, and in some cases, infections. Each of these in turn influence DNA methylation and other epigenetic processes. Therefore it’s not surprising, as our clinical experience bears out, that focusing on optimal DNA methylation using our program is generally helpful to both of these of all-too-common conditions of immune dysregulation.
In addition to being designed to sweet-talk DNA methylation, the Younger You program is also potently anti-inflammatory and hypoallergenic, healing to the microbiome, and low in sugar and simple carbs with time-restricted eating—all of these features make it an ideal foundational program for those suffering from allergies and autoimmunity. You may need further individualization of the program—for example, if you have an egg allergy, clearly those should be removed from the program. But in general, our clinical experience shows the Younger You Intensive to be very useful for folks with allergies and autoimmunity. The lifestyle pieces of the Younger You program are also essential, as stress has a significant negative impact on both allergies and autoimmunity, as do toxins.
Final thoughts
All of this points to one fact: a healthy diet and lifestyle unequivocally reduces incidence of many chronic diseases. This is great news. Whether you are fairly healthy or someone with a chronic condition (and perhaps wondering if it’s too late to change), it’s always a good time to support your DNA methylation and your bio age.
This blog was adapted from YOUNGER YOU by Dr. Kara Fitzgerald, courtesy of Hachette Book Group
Related content:
How Old Are You, Really?
Epinutrients – The Secret Ingredient That Makes Food Your Medicine
What is Biological Aging and What Does it Have to do with Methylation?
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Would you add cancer in this mix? Methylation influencing the growth of tumors?
Thank you for all the wonderful information you bring and share!
Absolutely! In fact, there is more data on cancer than other conditions. These are just six examples. – Team DrKF