114 | id == 114
114 | category_id == 15
114 | category_order == 11
114 | category_name == Diet
114 | category_color == #C47AC0
114 | slug == PPARA-keto-diet-saturated-fat
114 | title == Should You Avoid the Keto Diet & Saturated Fat? (PPARA, a Fat-Burning Gene)
114 | meta_description == PPARA is a fat-burning gene that might determine your ability to benefit from the keto diet. Are your genes keto-suited?
114 | summary == <p>The PPARA gene can rev up fat burning and metabolism. Certain variations may reduce PPARA activity, making a keto diet that&rsquo;s high in saturated fat a dangerous choice. Are your genes keto-suited?</p>
114 | overall_score_text == Your Keto Diet Suitability Score (based on PPARA)
114 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/PPARA--Diet-Keto-fat-burning.jpg
114 | author_id == 5
114 | author_name == Ana Aleksic
114 | author_title == MS (Pharmacy)
114 | author_order == 20
114 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Ana.jpg
114 | author_intro == <p><strong>Ana received her MS in Pharmacy from the University of Belgrade.</strong></p>    <p>Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.</p>
114 | reviewer == None
114 | medical_reviewer_id == 11
114 | medical_reviewer_name == Puya Yazdi
114 | medical_reviewer_title == MD
114 | publish_date == 2020
114 | publish_date == 3
114 | publish_date == 10
114 | avg_rating == 5.0
114 | tags_id == 297
114 | tags_name == Dietary fat
114 | tags_id == 305
114 | tags_name == Fat burning
114 | tags_id == 244
114 | tags_name == Fish oil
114 | tags_id == 301
114 | tags_name == Keto diet
114 | tags_id == 307
114 | tags_name == Lipid levels
114 | tags_id == 141
114 | tags_name == Metabolic Health
114 | tags_id == 300
114 | tags_name == PPAR-alpha
114 | tags_id == 306
114 | tags_name == Saturated fat
114 | permissions_favorite == False
114 | permissions_rate == False
114 | content_article == <h2><span style="font-weight: 400;">The PPARA Gene</span></h2> <p><a href="../../gene/ppara/"><span style="font-weight: 400;">The </span><em><span style="font-weight: 400;">PPARA gene</span></em></a><span style="font-weight: 400;"> is responsible for producing a protein called PPAR-&alpha; or </span><a href="https://selfhacked.com/blog/about-ppar-alpha-and-natural-ways-to-activate-it/"><span style="font-weight: 400;">PPAR alpha</span></a><span style="font-weight: 400;"> (short for peroxisome proliferator-activated receptor alpha) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">PPAR alpha is a key regulator of fat burning. More broadly, it controls energy balance and the metabolism of fats, carbohydrates, and amino acids [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">The </span><span style="font-weight: 400;">PPARA</span><span style="font-weight: 400;"> gene is important for determining your response to diet because PPAR alpha is under the strong influence of nutrients, especially fats. Its main natural activators are polyunsaturated fatty acids (PUFAs) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">When it comes to synthetic compounds, PPAR alpha is activated by drugs used to treat high blood fats (</span><em><span style="font-weight: 400;">dyslipidemias</span></em><span style="font-weight: 400;">). Other PPAR-alpha activators are being developed, which further emphasizes this protein&rsquo;s role in maintaining fatty acid balance in the body [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">PPARA is a key fat-burning gene that's under the strong influence of diet.&nbsp;</span></p> <h3><span style="font-weight: 400;">PPAR Alpha and the PPAR Family</span></h3> <p><span style="font-weight: 400;">PPAR alpha is part of the larger PPAR family, which also includes </span><a href="../../gene/pparg/"><span style="font-weight: 400;">PPAR gamma (PPARG)</span></a><span style="font-weight: 400;"> and </span><a href="../article/ppard-longevity-90"><span style="font-weight: 400;">PPARB/D (PPAR&beta;/&delta;)</span></a><span style="font-weight: 400;">.&nbsp;</span></p> <p><span style="font-weight: 400;">In general, PPARs bind to polyunsaturated fatty acids. However, different fatty acids activate different PPARs, triggering diverse downstream effects [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155092/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">For example, we know that PPAR alpha stimulates fat burning. But its close relative, PPAR gamma, seems to do the opposite. PPAR gamma helps preserve fat stores, making quick weight loss harder [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155092/"><span style="font-weight: 400;">R</span></a>,&nbsp;<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span><span style="font-weight: 400;">&nbsp;&nbsp;</span></p> <p><span style="font-weight: 400;">You can <a href="../article/pparg-weight-loss-mediterranean-diet-113">read more here</a> about how certain PPARG variations might help you lose weight on the Mediterranean diet.&nbsp;</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Although both belong to the same family, PPAR gamma appears to be a &ldquo;maintenance&rdquo; gene, whereas PPAR alpha is undoubtedly a metabolism-activating, catabolic one.</span></p> <h3><span style="font-weight: 400;">How PPAR Alpha May Rev Up Fat Burning</span></h3> <p><strong>PPAR alpha is found mostly in the liver and brown fat--the &ldquo;good&rdquo; fat that turns food into body heat.</strong><span style="font-weight: 400;"> Smaller amounts of PPAR alpha can also be expressed in the heart, kidneys, gut, and immune cells [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8536636"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Therefore, PPAR alpha seems to be strategically positioned to make us burn fat for energy. Fat burning starts in the liver, which releases energy and breakdown products into the bloodstream (via </span><em><span style="font-weight: 400;">fatty acid oxidation</span></em><span style="font-weight: 400;">)&nbsp; [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8536636"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28077274/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;&nbsp;</span></p> <p><span style="font-weight: 400;">The fat-burning process is continued in brown fat tissue, which is packed with </span><a href="https://www.selfhacked.com/blog/mitochondria/"><span style="font-weight: 400;">mitochondria</span></a><span style="font-weight: 400;">. As the end result, these dense mitochondria effectively turn calories from the liver&rsquo;s fat breakdown products into heat [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8536636"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28077274/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">This hints at PPAR alpha&rsquo;s role in ketosis--and individual differences in response to ketogenic diets.&nbsp;</span></p> <h3><span style="font-weight: 400;">PPAR Alpha Enables Ketosis</span></h3> <p><span style="font-weight: 400;">PPAR alpha can be activated when the body turns to burning fat for energy. Normally, we mainly burn carbohydrates for energy. The switch to burning fat as the primary energy source happens only during </span><a href="http://selfhacked.com/blog/intermittent-fasting/"><span style="font-weight: 400;">fasting</span></a><span style="font-weight: 400;"> or starvation, caloric restriction, and carbohydrate restriction (as on the keto diet) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/books/NBK499830/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">When the body needs to break down fat for energy, fat tissues release fatty acids. These fatty acids travel to PPAR alpha in the liver and immune cells. In turn, </span><strong>PPAR alpha enhances the production of ketone bodies--the key step to entering </strong><strong><em>nutritional ketosis</em></strong> <span style="font-weight: 400;">[</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/books/NBK499830/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">If PPAR alpha is not functioning well, fat burning and ketone body production may become impaired [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/books/NBK499830/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Recent experiments suggest that dietary fats are stronger activators of liver PPAR alpha than the fatty acids released from fat tissue. This might mean that ketogenic diets activate PPAR alpha better than fasting or caloric restriction does, but clinical evidence is still lacking to back up the link [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Good PPAR alpha activity helps the body burn fat for energy and enter nutritional ketosis.&nbsp;</span></p> <h3><span style="font-weight: 400;">Does PPAR Alpha Make the Keto Diet Anti-Inflammatory?</span></h3> <p><span style="font-weight: 400;">As part of this ketogenic pathway, PPAR alpha activation may also block inflammatory signals like </span><a href="https://selfhacked.com/blog/nuclear-factor-kappa-b/"><span style="font-weight: 400;">NF-kB</span></a><span style="font-weight: 400;">. Thus, PPAR alpha is often described as an anti-inflammatory protein [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10542237/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981249/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;&nbsp;</span></p> <p><span style="font-weight: 400;">This mechanism might, at least in part, also explain the proposed anti-inflammatory and antioxidant effects of the keto diet [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10542237/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981249/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;&nbsp;</span></p> <p><span style="font-weight: 400;">Indeed, drugs that activate PPAR alpha (fibrates) seem to reduce both blood lipids and blood vessel inflammation. Researchers suspect that the reverse is also true: poor PPAR alpha function may trigger or worsen inflammation. However, we need more human studies to know this for certain [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10542237/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <h2><span style="font-weight: 400;">PPARA Variations, Diet, and Health: An Overview</span></h2> <p><span style="font-weight: 400;">Given PPAR alpha&rsquo;s involvement in fat metabolism and energy balance, associations between PPARA genetic variants and abnormal lipid levels (dyslipidemia), heart disease, and type 2 diabetes do not come as a big surprise. Yet many of these associations remain to be confirmed in larger studies [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Scientists are optimistic that they&rsquo;ll be able to identify ways to personalize dietary recommendations by studying the interactions between PPARA genetic variants and the response to different diets&nbsp; [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;&nbsp;&nbsp;</span></p> <p><span style="font-weight: 400;">So far, the most well-studied PPARA SNP in nutrigenomics is </span><a href="../../snp/rs1800206/"><span style="font-weight: 400;">rs1800206</span></a><span style="font-weight: 400;">.&nbsp;</span></p> <p><strong>The less common (minor) G allele of rs1800206 (also known as the</strong><strong><em> L162V polymorphism</em></strong><strong>) reduces PPAR alpha activity</strong><span style="font-weight: 400;">, according to the available data [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;&nbsp;</span></p> <p><span style="font-weight: 400;">Carrying the G allele (GG or GC genotypes) has been associated with [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/%5C"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Increased heart disease risk in whites, with higher levels of triglycerides, total cholesterol, </span><a href="https://www.selfhacked.com/blog/ldl-cholesterol/"><span style="font-weight: 400;">LDL</span></a><span style="font-weight: 400;"> cholesterol, apoA1, and apoB and decreased levels of </span><a href="https://www.selfhacked.com/blog/hdl-cholesterol/"><span style="font-weight: 400;">HDL</span></a></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Poor response to saturated fat, which worsens heart disease risk, making ketogenic diets high in saturated fat a dangerous choice</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Beneficial response to polyunsaturated fatty acids (especially omega-3s/fish oil), which may support heart health and general well-being</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Possible, but uncertain impact on diabetes development</span></li> </ul> <p><span style="font-weight: 400;">The negative effects of this genotype seem to be more pronounced in men than in women and in whites than in Asians. Data on other ethnicities are sparse [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">G-allele carriers of rs1800206 might have trouble entering ketosis, possibly due to lower PPARA activity.&nbsp;&nbsp;</span></p> <p><span style="font-weight: 400;">Please have in mind that many other genetic and non-genetic factors also influence a person&rsquo;s response to diet and different nutrients. Additionally, remember that dietary interventions should always be part of a holistic approach to health that also takes lifestyle factors and your medical conditions into account.&nbsp;</span></p> <p><span style="font-weight: 400;">With this in mind, let&rsquo;s take a look at the specific dietary modifications that each genotype might benefit from--and how the keto diet plays in.&nbsp;</span></p> <h2><span style="font-weight: 400;">How PPARA Variations Affect Fat Breakdown &amp; Keto Diet Suitability</span></h2> <h3><span style="font-weight: 400;">Keto-Suited? Response to Total and Saturated Fat Intake</span></h3> <p><span style="font-weight: 400;">A study of 674 participants found that PPARA rs1800206</span><strong> G-allele carriers seem to do worse on a diet high in total and saturated fat </strong><span style="font-weight: 400;">(7% or more of daily energy intake) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21487230?dopt=Abstract"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Specifically,</span><strong> people carrying at least one G allele who consumed high amounts of saturated fat had smaller LDL particles than those with lower intakes, putting them at a greater risk of heart disease</strong><span style="font-weight: 400;">. Smaller, densely packed LDL particles are considered to be more dangerous and worse for heart health than bigger particles.&nbsp;</span></p> <p><span style="font-weight: 400;">Before the importance of LDL density was discovered, saturated fat was unfairly demonized. Research then revealed that low-carb diets high in saturated fat--similar to most paleo-style, high-protein keto diets--do increase total LDL. But this turned out to be entirely due to an increase in large, less dangerous LDL particles [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491165/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Further studies opened more questions, and the whole saturated fat dispute remains unresolved. For example, researchers showed that a diet low in carbs and high in saturated fat and beef protein may increase LDL particles across the full size spectrum [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491165/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Nonetheless, higher saturated fat intake is mainly linked with more large, &ldquo;good&rdquo; LDL particles in </span><em><span style="font-weight: 400;">most people</span></em><span style="font-weight: 400;">, according to the evidence. Genetics is there to fill in the gap and give us clues about what people who don&rsquo;t fit into the &ldquo;normal&rdquo; majority should do [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491165/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">And based on the data we have,</span><strong> carriers of the less common G allele (GG or GC genotypes) don&rsquo;t seem to be well suited for a </strong><a href="https://selfhacked.com/blog/ketogenic-diet-ketosis-health-benefits-physiology-genetics/"><strong>ketogenic diet</strong></a><strong> that is high in saturated fat</strong><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21487230?dopt=Abstract"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The opposite may be true for </span><strong>CC carriers, the majority, who may indeed reap the benefits of saturated fat.</strong><span style="font-weight: 400;"> Therefore, most people seem to be well suited for ketogenic diets [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21487230?dopt=Abstract"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Among people with the CC genotype, those with higher saturated fat intakes had larger LDL particles than those with lower saturated fat intakes. Thus,</span><strong> CC carriers were somewhat protected against heart disease--at least when it comes to LDL density--with higher saturated fat intake</strong><span style="font-weight: 400;">.&nbsp;</span></p> <p><span style="font-weight: 400;">Hypothetically, the observed effects might be explained by varying PPAR alpha function.&nbsp;</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">CC rs1800206 carriers might be more efficient at burning fat and generating ketones for energy. This process may also support heart health and general well-being by activating anti-inflammatory pathways, but more research is needed.</span></p> <h3><span style="font-weight: 400;">Potential Keto Diet Modifications: PUFA Intake &amp; Heart Health&nbsp;</span></h3> <p><span style="font-weight: 400;">A pivotal analysis that included 2373 people from the Framingham Offspring Study stresses the importance of PUFAs for carriers of the rare PPARA rs1800206 allele.&nbsp;</span></p> <p><span style="font-weight: 400;">This analysis initially found an association between the G allele of rs1800206 and higher total and LDL cholesterol in men and </span><a href="https://selfhacked.com/blog/apolipoprotein-b/"><span style="font-weight: 400;">apolipoprotein B</span></a><span style="font-weight: 400;"> in both genders. The LDL cholesterol link was even stronger in carriers of the &ldquo;good&rdquo; E2 </span><a href="../article/longevity-apoe-48"><span style="font-weight: 400;">APOE</span></a><span style="font-weight: 400;"> allele, suggesting close relationship between these two genes [</span><a href="https://www.ahajournals.org/doi/full/10.1161/01.atv.0000012302.11991.42"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">A follow-up study investigated how dietary fat intake might affect this association. They included 2106 people from the same cohort and concluded that G-allele carriers had greater triglyceride and apoC-III levels when they consumed a low-PUFA diet (6% or less of energy from PUFAs). But when their PUFA intake was high, they had </span><em><span style="font-weight: 400;">lower </span></em><span style="font-weight: 400;">triglyceride and apoC-III levels. ApoC-III is an emerging marker of heart disease and high triglycerides [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15735069/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://lipidworld.biomedcentral.com/articles/10.1186/s12944-016-0352-y"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><strong>The authors pointed out that the more PUFAs G-allele carriers ate, the more their triglycerides and apoC-III levels dropped</strong><span style="font-weight: 400;">--and vice versa: the lower their PUFA intake, the more these markers spiked.&nbsp;</span></p> <p><span style="font-weight: 400;">For example, when the diets of G-allele carriers had &lt;4% PUFA out of total calories, their triglycerides were about 28% higher than the levels in CC carriers. But when PUFA their intake was &gt;8%, they had 4% lower triglycerides than their CC counterparts. The same was true for both </span><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">omega-3</span></a><span style="font-weight: 400;"> and omega-6 fatty acids--the two main PUFA classes.</span></p> <p><span style="font-weight: 400;">Theoretically,</span><strong> a higher PUFA intake might make up for lower PPARA activity in G-allele carriers</strong><span style="font-weight: 400;">. Many other factors might explain this link too, and more research is needed to better understand them.&nbsp;</span></p> <p><strong>All in all, people carrying the less common G allele do better on a diet high in PUFAs: omega-3 and omega-6 fatty acids. </strong><span style="font-weight: 400;">They can still consume a modified, Mediterranean-style keto diet, but they don&rsquo;t do well when their diet is poor in PUFAs.</span><strong>&nbsp;&nbsp;</strong></p> <p><span style="font-weight: 400;">Omega-3s from fish are especially important since they&rsquo;re known to be heart-healthy and anti-inflammatory. Most Western diets lack omega-3 fatty acids and overabound in omega-6 fatty acids, which might worsen inflammation [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12442909"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><strong>A diet high in omega-3 PUFAs is still the healthiest choice even for people carrying the more common CC genotype.</strong><span style="font-weight: 400;"> However, these studies only suggest that CC carriers might be less prone to triglyceride spikes if their diet happens to be a bit lower in PUFAs, as most diets that rely on animal fat are [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21835413%5C"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;&nbsp;</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">People with the more common PPARA SNP were less likely to get high triglycerides from a variety of fats, while those with the less common variants required more PUFAs (omega-3s like fish oil).</span></p> <h3><span style="font-weight: 400;">Limitations&nbsp;</span></h3> <p><span style="font-weight: 400;">More research is needed to understand how gender impacts this genetic variation. Based on the existing data, the negative impact of the rare G allele of PPARA rs1800206 may be more pronounced in men.&nbsp;</span></p> <p><span style="font-weight: 400;">In the Framingham Offspring Study, the G allele was associated with raised total and LDL-cholesterol and apo B levels in men. In women, only the apoB rise was statistically significant. Similar gender differences were reported in another Canadian study [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <h3><span style="font-weight: 400;">PPAR Alpha&rsquo;s Downstream Genetic Effects</span></h3> <p><span style="font-weight: 400;">As one of the main switches for fat balance in the body, PPARA can influence many other genes. These include genes involved in fat transport (<a href="../../gene/apoa1/" target="_blank" rel="noopener">APOA1</a>, <a href="../../gene/apoa2/" target="_blank" rel="noopener">APOA2</a>, and <a href="../../gene/apoa5/" target="_blank" rel="noopener">APOA5</a>), fat burning (CPT-I, <a href="../../gene/cpt2/" target="_blank" rel="noopener">CPT-II</a>, delta-6-desaturase), HDL metabolism (<a href="../../gene/pltp/" target="_blank" rel="noopener">PLTP</a>), and </span><span style="font-weight: 400;">ketone</span><span style="font-weight: 400;"> production (</span><a href="https://www.selfdecode.com/gene/HMGCS2/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">HMGCS2</span></a><span style="font-weight: 400;">) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h2><span style="font-weight: 400;">Your PPARA Results for Keto Diet Suitability&nbsp;</span></h2> <p><span style="font-weight: 400;">You can see your genotypes for the main PPARA SNP in the table below. However, keep in mind that these results are based purely on association studies, and much more research will be needed to know what role&mdash;if any&mdash;these variants play in actually directly impacting a person&rsquo;s response to diet.</span></p> <p><span style="font-weight: 400;">By extension, just because a person might have some &ldquo;risk-associated&rdquo; genotypes for some of these SNPs does not necessarily mean that they will actually develop the health condition associated with it!</span></p> <p><span style="font-weight: 400;">This is because there are many different genetic, lifestyle, and environmental factors that can affect lipid levels, heart health, and diet compatibility. In other words, having a &ldquo;bad&rdquo; PPARG genotype does not necessarily predict anything specific about a person&rsquo;s response to diet&mdash; rather, these results illustrate just one of the many different genetic factors potentially related to it.</span></p> <p><span style="font-weight: 400;">With that in mind, the following table summarizes your results for the main PPARG SNP that have been linked to the health effects of a ketogenic diet high in saturated fat:</span></p> <p><span style="font-weight: 400;">*6858291142990616*</span></p> <h3><span style="font-weight: 400;">SNP Summary and Table</span></h3> <p><strong>Primary SNP: PPARA rs1800206&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;CC&rsquo; = Well suited for the keto diet; good response to most types of fat, including saturated fat and omega 3s/fish oil.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;CG&rsquo; and &lsquo;GG&rsquo; = Not well suited for a keto diet high in saturated fat; good response to PUFAs like omega 3s/fish oil.&nbsp;</span></li> </ul> <h3><span style="font-weight: 400;">Population Frequency</span></h3> <p><span style="font-weight: 400;">Overall, about 96% of the worldwide population have the CC genotype for rs1800206, 4% have the CG genotype, and only 0.2% have GG. The GG genotype is so rare that it&rsquo;s sometimes not even reported, and CG and GG genotypes are always viewed together in studies.&nbsp;</span></p> <p><span style="font-weight: 400;">There are some interesting differences across ethnicities. To break the numbers down:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">No East Asians or Peruvians seem to carry the G allele (100% are CC)</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Only 1% of Africans are CG or GG</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">About 5% of South Asians are CG or GG</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Around 6% of Latin Americans are CG or GG</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">11% of people of European descent are CG or GG</span></li> </ul> <p><span style="font-weight: 400;">Also, around 11% of people in Columbia have the CG genotype.&nbsp;</span></p> <p><span style="font-weight: 400;">There are some exceptions among South Asians: approximately 7% of Punjabi and 8% Sri Lankan Tamil populations are CG.&nbsp;</span></p> <p><span style="font-weight: 400;">Among Europeans, about 14% of British people, 19% of the Iberian population in Spain and 9% of people living in Tuscany (Italy) have the CG genotype.&nbsp;</span></p> <p><span style="font-weight: 400;">*7007115889548976*</span></p> <h2><span style="font-weight: 400;">Recommendations to Optimize the Keto Diet</span></h2> <p>*1236304060189537*</p> <h3><span style="font-weight: 400;">Diet</span></h3> <p><span style="font-weight: 400;">As discussed, </span><strong>people with the CC genotype for PPARA rs1800206 may do better on a keto diet that is relatively high in saturated fat.&nbsp;</strong></p> <p><span style="font-weight: 400;">The typical ketogenic diet is high in fats, moderate in proteins, and very low in carbohydrates. According to general ketogenic diet guidelines, you should get [</span><a href="https://www.ncbi.nlm.nih.gov/books/NBK499830/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">55% to 60% of energy from fat (60-70% on the Atkins keto diet)</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">30% to 35% of energy from protein (20-30% protein on the Atkins keto diet)</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">5% to 10% of energy from carbohydrates (20-50 g/day in a 2000 kcal per day diet)</span></li> </ul> <p><span style="font-weight: 400;">Various modifications to the standard ketogenic diet are possible. The general keto diet guidelines don&rsquo;t specify the type of fat, protein, or carbohydrate that people should consume.</span></p> <p><span style="font-weight: 400;">The typical keto diet is mixed-fat, which means that it includes a combination of saturated, monounsaturated (MUFAs), and polyunsaturated fats (PUFAs).&nbsp;</span></p> <h4><span style="font-weight: 400;">Gene-Based Modifications</span></h4> <p><strong>People with the CC PPARA rs1800206 genotype will likely to do better with saturated fat, such as:</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Grass-fed fatty meat&nbsp;</span></li> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/benefits-of-coconut-oil/"><span style="font-weight: 400;">Coconut oil</span></a></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Butter or </span><a href="http://selfhacked.com/blog/ghee-vs-coconut-oil/"><span style="font-weight: 400;">ghee</span></a></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Pork fat/lard</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Beef fat/tallow</span></li> </ul> <p><span style="font-weight: 400;">It&rsquo;s still a good idea for CC carriers to include a variety of fats, especially omega-3s. Most people will benefit from getting enough omega-3s, which are known to support heart health and wellness.&nbsp;</span></p> <p><span style="font-weight: 400;">On the contrary, </span><strong>people with the CG or GG PPARA rs1800206 genotype will probably do better by reducing saturated fat and increasing PUFAs.&nbsp;</strong></p> <p><span style="font-weight: 400;">If you carry this genotype (CG or GG), saturated fat should make up less than 7% (but ideally 4% or less) of your total daily energy intake. Your PUFA intake should reach at least 8% of your total daily energy.&nbsp;</span></p> <p><strong>Omega-3s </strong><span style="font-weight: 400;">are the healthiest type of PUFA and some good sources are:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">Fatty fish and seafood like salmon, mackerel, sardines, oysters, and caviar</span></li> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/hemp-seeds/"><span style="font-weight: 400;">Hemp seeds</span></a><span style="font-weight: 400;">, a good plant-based source&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Grass-fed beef, a decent animal-based source [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">The studies we brought up in this article lumped all PUFAs together, without discriminating between omega-3 and omega-6 fats. But since our diets are much higher in omega-6s, most people should favor omega-3 foods as a source of PUFAs. It&rsquo;s still ok to eat </span><strong>healthy omega-6 foods</strong><span style="font-weight: 400;"> like walnuts, eggs, and unprocessed sunflower oil and other vegetable oils in moderation.&nbsp;&nbsp;</span></p> <p><strong>CG and CG carriers might also benefit from reducing total daily fat intake</strong><span style="font-weight: 400;">. They are likely better suited for a modified Mediterranean-style diet that is generally healthy, moderately high in total fat (35% of energy from fat), and low in saturated fat. More research is needed to confirm this.&nbsp;</span></p> <h3><span style="font-weight: 400;">Supplements</span></h3> <p><span style="font-weight: 400;">Human studies have yet to test exactly which food and herbal compounds can activate PPAR alpha. Animal and cell-based studies point to the following compounds as potential candidates:</span></p> <ul> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/astaxanthin/"><span style="font-weight: 400;">Astaxanthin</span></a><span style="font-weight: 400;">, a red-colored carotenoid that&rsquo;s high in wild-caught fish and seafood [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Polyphenols like </span><a href="https://selfhacked.com/blog/top-15-scientific-health-benefits-of-resveratrol-with-references/"><span style="font-weight: 400;">resveratrol</span></a><span style="font-weight: 400;">, which is found in small quantities grapes, peanuts, and berries [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Arjunolic acid, a compound found in herbs traditionally used to support heart health like arjuna (</span><em><span style="font-weight: 400;">Terminalia arjuna</span></em><span style="font-weight: 400;">) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">An unsaturated fatty acid extracted from tomatoes [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></li> </ul> <p><span style="font-weight: 400;">PPAR alpha activators would be hypothetically beneficial for people with GC and GG PPARA rs1800206 genotypes. More research on this interaction is needed.&nbsp;</span></p> <h3><span style="font-weight: 400;">Drugs</span></h3> <p><span style="font-weight: 400;">If your triglyceride or cholesterol levels are high, your doctor may recommend certain medications along with lifestyle and dietary changes. Work with your doctor to treat any underlying conditions causing your abnormal lipid levels.</span></p> <p><span style="font-weight: 400;">Drugs that can bind to and activate PPAR alpha are chemically similar to fatty acids and are called </span><strong><em>fibrates.</em></strong> <span style="font-weight: 400;">Fibrates are available only with a doctor&rsquo;s prescription. Do not take any drugs without talking to your healthcare provider.&nbsp;</span></p> <p><span style="font-weight: 400;">Some examples of fibrates include fenofibrate, gemfibrozil, and bezafibrate. These drugs lower blood triglyceride levels likely by increasing the breakdown of triglyceride-rich VLDL and reducing the liver's production of VLDL. Fibrates may also increase HDL, but they don&rsquo;t reduce LDL cholesterol [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]</span></p>
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rsIDs = rs1800206
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