Polyunsaturated fat (PUFAs), when incorporated into cell membranes, make cells more fluid, are chaotropic and disorderly and reduce their function (1). The increase in fluidity will allow more water, sodium, chloride, and calcium into the cell (edema), and lower intracellular potassium and magnesium and this will also destabilize the cell, and reduce cellular function (2). Metabolic processes cannot occur optimally in such an environment. This increase in fluidity increases excitation, and proliferation (tumor growth) or cell death. Like I discussed in Part 1, membranes that contain more saturated fats are more rigid and are more resistant to toxins (estrogen, prolactin, heavy metals, etc.), thus improving their function (3).
Energy (ATP), is made in the mitochondria of the cell. Glucose, fats and proteins are transported into the cytoplasm to undergo the process where it’s converted to energy or other proteins/components used for other cellular functions. Glucose, when present in the cytoplasm, are converted by the pathway glycolysis to pyruvate. When there is an elevation of free fatty acids in the blood, such as with diabetes, cancer and many other diseases, there will also be a lot of fatty acids in the cytoplasm. The fats will compete with glucose for oxidation via the Randle cycle, and the pyruvate will be converted to lactate, instead of being shuttled into the mitochondria to be used by the Kreb cycle. But when there is not a lot of fatty acids to compete with glucose, pyruvate will be converted to acetyl-CoA and be used in the Kreb cycle, which is the second step in oxidative metabolism. The electrons which are released during reactions in the Kreb cycle is then used in the electron transport chain, to generate energy, ATP. So energy metabolism for glucose consists of three parts: glycolysis, Kreb cycle, and electron transport chain.
The proper oxidation of glucose creates lots of ATP and more CO2 than fats, which are protective to the organism and have no side effects such as lipid peroxidation or as substrates for inflammatory pathways (via cyclooxygenase or lipoxygenase), such as PUFAs do.
PUFAs inhibit glucose metabolism and cellular function
PUFAs inhibit several enzymes in the glycolytic pathway, namely phosphofructokinase, fructose 1:6‐bisphosphatase and pyruvate dehydrogenase (by increasing adrenocorticotrophic hormone (ACTH), and pyruvate kinase). Without these enzymes, glucose conversion to pyruvate and pyruvate entry into the mitochondria cannot happen (4, 5, 6, 7, 8). More pyruvate is converted to lactate, in the presence of PUFAs, than SFAs, and lactate is a metabolic toxin (9).
PUFAs inhibit several steps in the Kreb cycle as well, such as malic enzyme and isocitrate dehydrogenase, thus reducing the amount of energy produced, and increasing fat synthesis.
PUFAs also inhibit the electron transport chain, complex I, II, III, IV (cytochrome C oxidase), and ATPase, thus reducing ATP production (10, 11). SFAs don’t have this inhibitory effect, and palmitic acid actually increases pyruvate dehydrogenase, thus increasing glucose utilization.
PUFAs, including omega 3, are toxic to the mitochondria and will increase membrane permeability, oxidative stress and the loss of anti-oxidant molecules (glutathione) and ATP. This will lead to an increase in the release of cytochrome C into the blood and apoptosis (programmed cell death) (12). But ATP is required for apoptosis, and because of low ATP production, the cells will die via necrosis, which promotes inflammation. If cytochrome C is present in the blood during a blood test, there will be cell damage and cell death happening somewhere in the body.
Rats fed a fat free diet are much learner, have higher oxidative capacities and have 70% faster metabolisms than rats that are fed fat.
In this study, a human subject, consumed 2500 calories and less than 2 grams of fat daily for 6 months (13). During this time his metabolism increased significantly, he lost weight, and he didn’t show any sign of skin defects (as a result of “essential fatty acids” deficiency). In contrast, he actually showed improvements in health, such as a disappearance of fatigue after a days work, elimination of periodic migraines, decrease in high blood pressure, not getting sick, reduced infection and improvements in skin and mucous membranes quality.
Inhibit mitochondrial multiplication
Luckily, our bodies can make new mitochondria to replace the old ones that are damaged or that has died. It’s called mitochondrial biogenesis, and it’s under the control of peroxisome proliferator–activated receptor γ coactivator-1 (PGC1α). PGC1α increases the transcription of enzymes necessary for substrate oxidation, electron transport and ATP synthesis and mitochondrial biogenesis. But PUFAs inhibit mitochondrial biogenesis by inhibiting PGC1α. A diet not even that high in fat, (35% of calories, of which 80% is PUFA) was able to reduce PGC-1α and PGC1β mRNA by 20% and 25%, respectively (14). Plus PUFAs inhibit enzymes in the body that breaks down damaged cells, thus allowing damaged cells to build up in the body, which eventually leads to disease, such as Alzheimer’s (tau protein and Aβ), diabetes (advanced glycation end products (AGE)), etc.
Inhibit normal thyroid function
- increase TSH and prolactin. Elevated TSH is associated with hypothyroid. TSH also increases COX and the release of arachidonic acid from cell membranes and thus inflammation (15).
- inhibit thyroid peroxidase (the enzyme in the thyroid that creates thyroid hormones), thus decreasing T4 and T3 production and T4 to T3 conversion in the liver (16).
- inhibit thyroid binding to its transport protein, thus preventing its transport in the body.
- inhibit thyroid hormone receptors, thus preventing thyroid hormones from exerting its actions (17, 18, 19, 20, 21, 22).
PUFAs, because of their unsaturation they have a higher affinity for thyroid and vitamin A transport protein, displace thyroid hormones from their transporting protein, and prevents thyroid hormones from entering cells. This means, that even when thyroid hormones appear normal on thyroid tests, you can still experience hypothyroid symptoms. Thyroid hormones are essential for energy and hormone production and vitality and much more.
PUFAs increase fat storage
When cellular function is inhibited by PUFAs, they cannot successfully make energy, and then the PUFAs are rather stored as fat. Hypometabolic people have a higher tendency to store fat than normal metabolic people, even while eating a lot less calories.
PUFAs not only slow the metabolism, but it also increases the enzymes that synthesize fat (fatty acid synthase).
PUFAs increase fat storage, by increasing adipose sensitivity to insulin and increasing the formation of new fat cells, via prostacyclin (23, 24). PUFAs promote fat storage not only in the adipose tissue, but also in the liver, muscles and other organs (25). This increase in fat storage in organs reduce the storage space for glucose and PUFAs also directly inhibit glycogen storage by inhibiting the enzymes glucokinase and glucose 6‐phosphatase.
Thirdly, PUFAs inhibit uncoupling (UCP1) and promotes obesity (26).
Arachidonic acid increases endocannabinoids, and an overactive endocannabinoid system plays a crucial role in obesity by increasing food intake and lipogenesis (which leads to fatty liver and steatosis), increasing gluconeogenesis (leading to high blood glucose), lowering GLUT4 (decreased glucose transport into cells), increasing inflammation (NF-κB), causing insulin resistance, and impairing suppression of liver glucose output (27, 28, 29). Using aspirin will block this effect of cannabinoid receptor activation, by inhibiting the JNK signaling pathway (30).
Stearic and palmitic acid are inhibitors of the enzyme fatty acid synthase (FAS) and do not promote adipose inflammation and expansion such as PUFAs (31).
If you want to lose fat, your insulin needs to be low, and for that, you need to be very insulin sensitive. PUFAs directly antagonize insulin receptor and cause hyperinsulinemia, which promotes fat storage and obesity.
PUFAs damage the beta-cells of the pancreas and prevents proper secretion of insulin. In animal study, when the animals were fed a fat-free diet, or a diet containing only saturated fat, with protein, vitamins and minerals, they couldn’t develop diabetes, even when the researchers damaged their beta-cells through various methods. The alpha cells of the pancreas can convert to beta cell in the presence of glucose, but is inhibited by PUFAs. PUFAs causes both diabetes type 1 & 2, by damaging the beta cells of the pancreas (32), and being PUFAs deficient prevents diabetes (33).
An increase in endocannabinoids, caused by arachidonic acid, contribute to diabetes, by increasing lipogenesis, gluconeogenesis, inulin resistance, fatty liver, etc.
Gluconeogenesis is three times as high in the average diabetic patient vs a normal individual, and PUFAs directly increase this pathway (34). Diabetic cells are in a constant need for sugar, but doesn’t sense the high blood sugar (because of insulin resistance), and then breaks the muscle down to make extra glucose. That’s one major reason why diabetes is such a wasting disease.
PUFAs also increase the formation of advanced glycation end-products (AGE) many times faster than sugar. CO2 protects the proteins, hemoglobin, from glycation (by binding to the lysine group), and PUFAs lower CO2 production, thus speeding up glycation (35). High fat/PUFAs diets are linked to the excess AGEs/advanced lipoxidation end products inherent in fatty diets (36, 37).
CO2 also protects against retina damage and nerve damage caused by diabetes, yet CO2 is not high enough, because diabetes waste glucose, by producing lactic acid. And PUFAs are one of the main causes of glucose wasting. And metformin, also increases lactic acid, indicating that it’s causing glucose to be wasted.
PUFAs also inhibits the insulin receptor, causes hyperinsulinemia, insulin resistance and destroys the beta-cells of the pancreas.
PUFAs will keep you in that hypometabolic state, by suppressing cellular function, increasing stress hormones and its own release and oxidation, inhibit glycogen storage and glucose oxidation, inhibit thyroid function and put you in a low energy state.
A low energy state is similar to aging, and when you are not producing enough energy, your body has to make choices where to partition the available energy. The brain is most important, so most of the glucose will go to the brain, yet reduced mental function is still a symptom of diabetes, indicating ineffective energy production. The first areas where your body will reduce energy production is the reproductive area, skin, hair, eyes, hearing, etc. You’ll basically feel older than what you are, because of a lack of energy induced by PUFAs.
Many people argue that they feel great on a high PUFA or ketogenic diet. This is mainly because PUFAs increase stress hormones (such as cortisol and adrenaline), which do a very good job at masking things that are going wrong. So in the short term, a few years at most, you might feel good, but then things start to go backward, and you start to notice symptoms of low energy, fatigue, sleep disturbance, cognitive dysfunction, high cortisol, serotonin, adrenaline, estrogen, etc.
Having a robust metabolism, oxidizing sugar, producing lots of CO2 (A), while having optimal thyroid and hormonal production is best maintained while minimizing PUFA intake and eat only saturated rich foods, such as dairy fat (butter, cream, ghee, cheese, etc.), beef, lamb, bison and game, goat, cocoa butter, MCT oil and coconut oil.
PUFAs inhibit cellular function, energy production, thyroid function, lead to cell death, hypoxia and these things will always lead to some kind of disease.