TRUTHITION

Polyunsaturated Fatty Acids: The Real Killer III

A deeper dive into the "good" and "bad" fatty acids.

January 20, 2025 Truthition Team

Introduction

In the previous section of this article, we discussed the various types of fats, as well as clinical trials and studies which concluded that polyunsaturated fatty acids (PUFAs) are either less conducive or not as beneficial to health as monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs). This included a basic overview of the chemical structures and examples of these fatty acids. It was also noted that throughout human history, the consumption of PUFAs—at least in their current composition—has been significantly lower than it is today. While clinical trials exist supporting both sides of the debate on the effects of PUFAs on health, this article will discuss the direct biochemical reasons regarding why PUFAs negatively affect human health. Additionally, we will review further clinical trials and research papers that support these findings. Specifically, PUFAs are not truly “essential” fatty acids, have adverse metabolic consequences, and have been linked to infertility, inflammation, and even cancer.

Brief Overview of Lipid Chemistry

To provide a foundation for this discussion, here is a brief overview of lipid chemistry. For the full context, refer to the earlier part of this article.

Lipids (fats) are generally classified into three main categories:

1. Saturated Fatty Acids (SFAs): These are the most chemically stable fats, featuring straight, “rigid” bonds.
2. Monounsaturated Fatty Acids (MUFAs): Slightly less stable than SFAs, these fats contain one double bond, creating a “kink” in the structure.
3. Polyunsaturated Fatty Acids (PUFAs): Being the least stable of the three, these fats have multiple (poly) double bonds that result in an unstable kinked molecular structure.

Polyunsaturated fats are further subcategorized into omega-3, omega-6, and omega-9, depending on their specific chemical structure. Among these, omega-3 and omega-6 fatty acids are often labeled as “essential fatty acids”—a designation that will be examined critically in the next section.

There are numerous types of fats that fall into each category, but the following is a table of the names for some of the fatty acids that may be mentioned in this article:

Why Essential?

It has been mentioned that Omega-6s and Omega-3s are considered “essential” fatty acids. This flattering title was awarded simply because the body is not able to synthesize them.^[23] This has allowed industries to promote their products and foods as inherently “essential” and, therefore, “healthy” or necessary. While the body cannot synthesize omega-6s or omega-3s, most of them are far from essential by many conventional definitions.

For example, linoleic acid (LA) is commonly accepted as an essential fatty acid; however, its essentiality is debatable. A 1990 analysis published in Lipids Vol. 25 focused their attention on the essentiality of different PUFAs in parts of the body. In the study, several types of PUFAs were observed in rats. When rats were fed 150mg of linoleic acid (LA) per 100g food consumption—approximately 0.3% of their calorie intake—there was “[no] effect on reproduction, gestation, perinatal mortality, body weight increase, or overall mortality”.^[24] This suggests that LA was not required for any of these functions in the rats. On the other hand, LA intake being 2.4% of calories was considered optimal for liver health in these rats. This equates to about 6.6g of linoleic acid for a human with a 2500 calorie diet. However, given that significantly lower intake levels did not impact reproduction, weight gain, or mortality, the rationale behind their higher “optimal” level remains unclear: it was not discussed in the paper.

With vegetable oils having an increased prevalence in the modern diet, humans get far more than “required” or even “optimal” according to this study. One example is soybean oil with approximately 50-60% linoleic acid content.^[25] Just one tablespoon of soybean oil is estimated to be about 7 grams of linoleic acid, already far surpassing this study’s baseline recommendation.

^{https://doi.org/10.1016/B978-1-78242-089-7.00015-4 [25]}

As stated in part 1, soybean oil has become the most prevalent vegetable oil in the processed food industry. Soybean oil has replaced healthier fat sources in numerous major foods, such as mayonnaise, where the most common commercially available mayonnaise is made with soybean oil. Being a western staple for sandwiches, salads, and other dishes, it is used frequently for many people. Just two tablespoons of mayonnaise contain approximately 11g of linoleic acid^[26]—well above the amount “required” for human health. The potential health consequences of such overconsumption will be explored in subsequent sections.

Low Essential Fatty Acid Diets in Humans

The trial described previously is applicable to rats, and, to some extent, human anatomy. The following research delves deeper in relevance to essential fatty acids (EFAs) and PUFAs in both animals and humans. A 1971 publication of Progress in the Chemistry of Fats and other Lipids raised a few interesting points. Due to the age of this publication and the studies cited, irrelevant trials or those relying on outdated methods were omitted.

There are some health and medical websites that promote fish oil supplementation due to their omega-3 fatty acid content and the associated supposed health benefits. However, there is evidence to suggest that not only do fish oils not have many of the supposed benefits some health communities claim (consult part 2), but they may be potentially toxic to the human body and other organisms. In numerous studies, cod liver oil has been shown to have toxic effects on many organisms—including humans—directly traced back to the lipid content.^[27] One study found that male rats fed a diet containing 29% cod liver oil had a significantly lower testes weight and were sterile compared to rats fed soybean oil.^[27]

In this publication, it was mentioned, relevantly, that much of the research on essential fatty acids (EFAs) is quite black-and-white, with groups being fed either a low-fat diet or a diet rich in EFAs. It is only natural that a diet deficient in a required macronutrient would be more toxic to organisms than a diet fed even almost exclusively the most harmful of that macronutrient—EFAs in this case. Much of the same research is prevalent to this day. This binary view may contribute to the favorable perception of PUFAs today.

One study discussed in the same publication noted increased metabolic function and weight loss in humans consuming a low-EFA diet. It has been frequently posited that, regarding lifespan, lower metabolic function is superior to higher metabolic function; however, this theory has been discredited by several studies. One such study published in Ecological and Evolutionary Physiology found that higher energy expenditure, and therefore higher metabolic function, had no difference in mortality with lower energy expenditure and lower metabolic function.^[28] The topic of nutrition and metabolism itself warrants an entire article for discussion. The point stands that loss of weight and a higher metabolism from a low-EFA diet are certainly not negative outcomes.

In another study discussed, C3H strain mice (genetically identical mice) were fed various types of fat. It concluded that survival decreased when increasing either the fat intake as a whole or the unsaturation of the fat in the diet. Similar studies on rats have also provided similar results.^[27] As peroxidation of PUFAs is well-known (and will be discussed), vitamin E was provided to the animals in an attempt to reduce oxidation. However, tumors cropped up often in the high-fat/high-unsaturated fat groups, and even correcting for mortality from tumors, it was found that these groups still had increased mortality. This suggests a potential correlation between PUFA and issues beyond cancer.

Lipid Peroxidation and Vitamin E Antioxidation

Polyunsaturated fatty acids are highly susceptible to oxidation, a process known as lipid peroxidation. Free radicals attack the double bonds in PUFAs, replacing hydrogen with oxygen and forming byproducts like malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Millions of free radicals are generated by the cell in a full day, many of which attack various parts of the body.^[29] These double bonds are a common and easy target for free radicals, making PUFA extremely vulnerable to these attacks.

Lipid peroxidation is harmful for several reasons, one being the secondary products formed during the process. MDA and 4-HNE are considered the most mutagenic and toxic secondary products respectively.^[29] Mutagenic means that these particles are prone to damaging a cell’s DNA, causing mutations that may or may not be cancerous. Common problems associated with MDA and 4-HNE include Alzheimer’s disease, cancer, cardiovascular disease, diabetes, liver disease, and Parkinson’s disease.^[29] It has been found that high levels of lipid peroxidation is associated with increased rates of self-induced cell death and considered toxic. Furthermore, lipid peroxidation of PUFAs is likely to be the primary reason that LDL cholesterol is considered “bad”, but that also warrants its own article for discussion. In contrast, SFAs and MUFAs are far less susceptible to lipid peroxidation.

Antioxidation of Vitamin E

In this context, however, antioxidants such as tocopherol (Vitamin E) can effectively reverse the effects of lipid peroxidation. It donates a hydrogen atom to these oxidated lipids, causing the formation of non-radical products instead.^[29] For instance, research has shown a direct relationship between the degree of unsaturation of dietary fat and the body's tocopherol requirements:

“The rate of development of creatinuria in tocopherol deficient rats is related to the degree of unsaturation of the dietary fat. As⁷ Rate of onset of creatinuria was parallel with the rates of oxidation of unsaturated acids, … Thus tocopherol requirement is related to fatty acid composition of the diet, or conversely, at constant tocopherol intake, increases in dietary polyunsaturated acids could be deleterious”.^[27]

This is stating that the direct unsaturation of dietary fat in this study is associated with creatinuria, a condition associated with kidney problems and metabolic issues.^[30] This appeared to maximize in effect in correlation to how quickly these lipids oxidized. Importantly, the damage caused by high PUFA intake and low antioxidant levels can be reversed by vitamin E supplementation. Another study shows that damage done from high PUFA and low antioxidants can be reversed with tocopherol:

“Sterility in male chickens can be induced by diets with a high content of linoleic acid and low content of vitamin E. After sterility is induced by this regimen, it can be reversed by re-supplementing with tocopherol,²² and semen production is improved by the supplementation”.^[27]

Such findings underscore the protective role of vitamin E in PUFA-rich diets. While adequate levels of vitamin E can reduce the harmful effects of lipid peroxidation, the most effective strategy remains limiting PUFA consumption altogether.

Essential Fatty Acids and Cancer

As discussed in part I of this article, cancer rates have been steadily increasing in recent years, as has PUFA intake. This correlation alone is not enough to villainize PUFAs, but there is some biochemical evidence to suggest that it might be a direct contributor to this rise. There are three main pathways that PUFA may be able to cause cancer.

• Lipid Peroxidation: The mutagenic secondary products of lipid peroxidation could cause damage to DNA, potentially leading to cancerous mutations.
• Inflammation: Being directly linked to cancer, among other conditions, anti-inflammatory drugs have been proposed and attempted to try to prevent cancer in high-risk individuals.^[31] Prostaglandins, fats that act similarly to hormones, play a key role in inflammation and cancer progression.^[32] Prostaglandin E2 (PGE2) is one prostaglandin that is associated with inflammation and thus tumor growth.^[33] PGE2 is metabolized from Arachidonic Acid (AA) by the COX-2 pathway.

Simply put, AA, an omega-6 PUFA, interacts with the cyclooxygenase-2 (COX-2) enzyme to produce PGE2.^[34] PGE2 is carcinogenic because it stimulates cell division, suppresses apoptosis (self-induced cell death), and promotes tumor angiogenesis, meaning it induces the creation of blood vessels throughout the tumor to connect to the main blood supply of the body.^[33] Linoleic Acid (LA), the most common form of omega-6, also metabolizes into Arachidonic Acid (AA), the primary fatty acid known to be responsible for this interaction.^[35]
Interestingly, in one trial, omega-3 fatty acids like Eicosapentaenoic acid (EPA) alone produced about one-third of these prostaglandins compared to AA.^[34] Based on this research, it appears this PGE2 production may be more sensitive to omega-6 PUFA than omega-3. However, it’s important not to absolve omega-3 entirely, as it, too, is subject to the same issues of lipid peroxidation and oxidative stress discussed earlier.
• UV Radiation: Another lesser-known issue is with the sun. While it is common to state that UV rays can cause sun burn and melanoma, it is not the only factor at play. According to cancer.gov, observed melanoma cases have risen by 3.1x from 1975 to 2021.^[36] In 1975, 8.78 per 100,000 cases were observed, and in 2021, a whopping 27.27 per 100,000 cases were reported. A plausible contributing factor may be the lipid peroxidation of PUFA underneath the skin, with UV exposure exacerbating the process. A 2014 analysis found that in UV exposed skin, free radical secondary products were significantly increased. Interestingly, with alpha-tocopherol (a form of vitamin E), they were significantly decreased.^[37] This and other pieces of evidence directly link UV radiation and lipid peroxidation. Seeing that an excess of PUFA intake definitively increases the prevalence of lipid peroxidation, it makes sense that even a small amount of UV exposure would be enormously dangerous to individuals with high-PUFA diets. This is one variable to explain why melanoma cases have gone up 3.1x when it appears that people are staying indoors and using sunscreen more than ever before.^[38] It is the same sun that humans have evolved with throughout history, but certainly not the same diet.

Conclusion

Putting the pieces together, the human diet has been changing at an unprecedented rate, with far more PUFA-rich products hitting the shelves, especially vegetable oils. It has been concluded that vegetable oils alone are certainly hazardous to human health, and this could be partially or entirely due to the polyunsaturated fatty acids. While PUFAs are essential in very small amounts, the typical Western diet contains far more than necessary, leading to various health issues.

Among these potential problems associated with PUFA consumption are inflammation via excess PGE2 production and lipid peroxidation, both of which are linked to diseases such as Alzheimer’s, various cancers, cardiovascular disease, diabetes, liver disease, and Parkinson’s disease. Both omega-6s and omega-3s are susceptible to lipid peroxidation, and neither should be consumed in excess, and in healthy humans, certainly not supplemented.

Polyunsaturated fatty acids should be consumed in strict moderation, and omega-3s and omega-6s should be balanced in equal ratios to mitigate their negative effects, as they displace each other within the body. Ideally, vegetable oils should be avoided entirely, and natural sources of PUFA should maintain balanced omega-3 and omega-6 ratios. To prevent problems associated with lipid peroxidation, vitamin E can be supplemented to lower the chances of PUFA doing harm caused by lipid peroxidation. Furthermore, there is a strong case for reevaluating the health risks associated with saturated fats, which will be addressed in a separate article. Considering the pervasive inclusion of omega-3 and omega-6 PUFAs in modern diets, a comprehensive reevaluation of their health implications is both timely and necessary. Understanding of these fats will be pivotal in shaping true evidence-based dietary guidelines that will promote improved public health for all.

Citations

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